An ab initio theoretical study of electronic structure and properties of 2'-deoxyguanosine in gas phase and aqueous media.
Molecular geometries of two structural forms of 2'-deoxyguanosine (keto-N9R and keto-N7R, R = the sugar moiety) considering both the C2'-endo and C3'-endo conformations of the sugar ring and those of the complexes of these species with two water molecules each were optimized employing the ab initio RHF procedure. A mixed basis set consisting of the 6-311+G* basis set for the nitrogen atom of the amino group and the 4-31G basis set for all the other atoms was used. The RHF calculations were followed by correlation correction of the total energy at the MP2 level. Both the structural forms of 2'-deoxyguanosine were solvated using the polarized continuum model (PCM) of the self-consistent reaction field (SCRF) theory and the corresponding RHF optimized geometries at the RHF and MP2 levels. Geometry optimization was also performed in aqueous media using the Onsager model at the RHF level using the above-mentioned mixed basis set, and subsequently, using the reoptimized geometries, single-point MP2 calculations were performed. It is found that both the keto-N9R and keto-N7R forms of 2'-deoxyguanosine as well as their complexes with two water molecules each would occur, particularly at the water-air interface. Though the normal Watson-Crick-type base pairing would not be possible with the keto-N7R form of 2'-deoxyguanosine(G*), two other (G*-C and G*-T) base pairing schemes may occur with this form of the nucleoside, which may cause mutation. The present calculated geometry of the keto-N9R form of the anti-conformation of 2'-deoxyguanosine including the dihedral angle chi(CN) agree satisfactorily with the available crystallographic results. The present results also agree satisfactorily with those obtained by other authors earlier for the keto-N9R form of 2'-deoxyguanosine using B3LYP and MP2 methods employing the 6-31G* basis set. Using transition state calculations, it is shown that tautomerism of guanine and other similar molecules where the tautomers would coexist would be facilitated by the occurrence of the H(+) and OH(-) fragments of water molecules. Further, this coexistence of the two tautomers appears to make the C8 carbon atom located between the N7 and N9 nitrogen atoms susceptible to attack by the OH(-) group. Thus, an explanation is obtained for the efficient formation of the reaction product 8-hydroxy-2'-deoxyguanosine, which serves as a biomarker for oxidative damage to DNA in biological systems.


Effect of dietary excess-histidine on fructose 1,6-bisphosphatase and 6-phosphofructokinase activities, and activation of fructose 1,6-bisphosphatase by basic amino acids in rat liver.
1. Dietary excess histidine caused an increase in the total activity of fructose 1,6-bisphosphatase, and a decrease in 6-phosphofructokinase in the liver. 2. The hepatic concentrations of free histidine and lysine were higher in rats fed a histidine-excess diet. 3. The addition of histidine, lysine or arginine to the assay mixture for fructose 1,6-bisphosphatase resulted in a significant increase in its activity. The 6-phosphofructokinase activity in the liver was not enhanced by the addition of histidine to the assay mixture.


[Corticosteroid therapy and therapeutic education: experience of an internal medicine department].
In 2003, we sought to determine what were the needs of patients prescribed with long-term glucocorticoid therapy in our internal medicine department. Following this inventory, we decided to homogenize the medical practices regarding glucocorticoid prescriptions in our institution. We also set up a therapeutic educational program focused on these prescriptions. This program is based both on individual and collective sessions. Its aims are to improve patients' autonomy regarding the glucocorticoid therapy and to improve the quality of care. This program has widely favored discussions within the medical team and has contributed to enrich experience and expertise of each of its member. We believe it has improved both the satisfaction of the patients and the medical staff.


Efficacy, safety and cost-efficiency of using an alternative technique for automated exchange transfusion in pediatric patients with sickle cell disease.
Sickle cell disease (SCD) patients suffer complications requiring simple and/or exchange transfusion. In 1999 we developed an automated exchange technique using infusion pumps and vascular catheters (IV Pump Method). To prove that IV Pump Method is cost-efficient, and as safe and effective as automated cell separators. Retrospective chart review of SCD patients requiring exchange transfusion admitted to PICU from 2003-2009. Evaluated method used, complications, costs, and Hemoglobin S% (HgS%) change, excluding patients not requiring exchange transfusion. Cost-reduction with IV Pump Method is around $1000. Average HgS% reduction using IV Pump Method was 30.3 vs. 28.8 in Blood Cell Separator group (p = 0.84). We had no complications or mortalities, with the majority of patients being male (p = 0.03) and on the oldest age group (11-19 y/o) for both methods. The IV Pump Method is a safe, effective, and cost-efficient alternative to perform exchange transfusion.


The rate of internalization of the mannose 6-phosphate/insulin-like growth factor II receptor is enhanced by multivalent ligand binding.
The cation-independent mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF-II receptor) undergoes constitutive endocytosis, mediating the internalization of two unrelated classes of ligands, mannose 6-phosphate (Man-6-P)-containing acid hydrolases and insulin-like growth factor II (IGF-II). To determine the role of ligand valency in M6P/IGF-II receptor-mediated endocytosis, we measured the internalization rates of two ligands, beta-glucuronidase (a homotetramer bearing multiple Man-6-P moieties) and IGF-II. We found that beta-glucuronidase entered the cell approximately 3-4-fold faster than IGF-II. Unlabeled beta-glucuronidase stimulated the rate of internalization of 125I-IGF-II to equal that of 125I-beta-glucuronidase, but a bivalent synthetic tripeptide capable of occupying both Man-6-P-binding sites on the M6P/IGF-II receptor simultaneously did not. A mutant receptor with one of the two Man-6-P-binding sites inactivated retained the ability to internalize beta-glucuronidase faster than IGF-II. Thus, the increased rate of internalization required a multivalent ligand and a single Man-6-P-binding site on the receptor. M6P/IGF-II receptor solubilized and purified in Triton X-100 was present as a monomer, but association with beta-glucuronidase generated a complex composed of two receptors and one beta-glucuronidase. Neither IGF-II nor the synthetic peptide induced receptor dimerization. These results indicate that intermolecular cross-linking of the M6P/IGF-II receptor occurs upon binding of a multivalent ligand, resulting in an increased rate of internalization.


TNF-a stimulation enhances ROS-dependent cell migration via NF-?B activation in liver cells.
Development of hepatocellular carcinoma (HCC) is accompanied by a continuous increase in generation of reactive oxygen species (ROS). TNF-a was used in murine hepatocytes as stimulus to identify the primary source of ROS generation. Using specific inhibitors targeting the different complexes of the respiratory chain we detected the mitochondria as main producer of ROS. TNF-a altered mitochondrial integrity by mimicking a mild uncoupling effect in liver cells. siRNA mediated downregulation of essential assembly factors for complex I and complex III led to an inhibition of ROS production. Therefore, ROS is generated by the mitochondrial respiratory chain upon TNF-a stimulation. ROS activated NF-?B and subsequently enhanced migration of liver cells. Thus, we identified complex I and complex III of the respiratory chain as point of ROS release after TNF-a treatment in hepatocytes which enhances cell migration by activating NF-?B signaling.


Pregnancy in women with bladder exstrophy.
Little is known about pregnancies in women with bladder exstrophy. Of 28 women with bladder exstrophy who were evaluated 7 became pregnant and 5 delivered successfully. Problems seen during pregnancy, the long-term effects and the need for early, informed counseling by the urologist are discussed.


Educational inequality in multimorbidity: causality and causal pathways. A mendelian randomisation study in UK Biobank.
Multimorbidity, typically defined as having two or more long-term health conditions, is associated with reduced wellbeing and life expectancy. Understanding the determinants of multimorbidity, including whether they are causal, may help with the design and prioritisation of prevention interventions. This study seeks to assess the causality of education, BMI, smoking and alcohol as determinants of multimorbidity, and the degree to which BMI, smoking and alcohol mediate differences in multimorbidity by level of education. Participants were 181,214 females and 155,677 males, mean ages 56.7 and 57.1 years respectively, from UK Biobank. We used a Mendelian randomization design; an approach that uses genetic variants as instrumental variables to interrogate causality. The prevalence of multimorbidity was 55.1%. Mendelian randomization suggests that lower education, higher BMI and higher levels of smoking causally increase the risk of multimorbidity. For example, one standard deviation (equivalent to 5.1 years) increase in genetically-predicted years of education decreases the risk of multimorbidity by 9.0% (95% CI: 6.5 to 11.4%). A 5 kg/m2 increase in genetically-predicted BMI increases the risk of multimorbidity by 9.2% (95% CI: 8.1 to 10.3%) and a one SD higher lifetime smoking index increases the risk of multimorbidity by 6.8% (95% CI: 3.3 to 10.4%). Evidence for a causal effect of genetically-predicted alcohol consumption on multimorbidity was less strong; an increase of 5 units of alcohol per week increases the risk of multimorbidity by 1.3% (95% CI: 0.2 to 2.5%). The proportions of the association between education and multimorbidity explained by BMI and smoking are 20.4% and 17.6% respectively. Collectively, BMI and smoking account for 31.8% of the educational inequality in multimorbidity. Education, BMI, smoking and alcohol consumption are intervenable causal risk factors for multimorbidity. Furthermore, BMI and lifetime smoking make a considerable contribution to the generation of educational inequalities in multimorbidity. Public health interventions that improve population-wide levels of these risk factors are likely to reduce multimorbidity and inequalities in its occurrence.


A re-evaluation of song development in the song sparrow.
Song sparrows were hand-reared from the egg in auditory isolation from adult conspecifics and maintained either together with other species or individually in sound chambers. Songs developed by the males contained several normal species-specific characteristics, but on the whole differed both qualitatively and quantitatively and were therefore readily distinguished from wild-type songs. The data are largely consistent with those of Mulligan (1966), but the normal aspects of song development have been over-emphasized in recent literature.


Effect of nicotinamide adenine dinucleotide on the membrane-associated reduced nicotinamide adenine dinucleotide oxidase of Mycobacterium phlei.
NAD+ had a biphasic effect on the NADH oxidase activity in electron transport particles from Mycobacterium phlei. The oxidase was inhibited competitively by NAD+ at concentrations above 0.05 mM. NAD+ in concentrations from 0.02 to 0.05 mM resulted in maximum stimulation of both NADH oxidation and oxygen uptake with concentrations of substrate both above and below the apparent K-M. Oxygen uptake and cyanide sensitivity indicated that the NAD+ stimulatory effect was linked to the terminal respiratory chain. The stimulatory effect was specific for NAD+. NAD+ was also specific in protecting the oxidase during heating at 50 degrees and against inactivation during storage at 0 degrees. NAD+ glycohydrolase did not affect stimulation nor heat protection of the NADH oxidase activity if the particles were previously preincubated with NAD+. Binding studies revealed that the particles bound approximately 3.6 pmol of [14C1NAD+ per mg of electron transport particle protein. Although bound NAD+ represented only a small fraction of the total added NAD+ necessary for maximal stimulation, removal of the apparently unbound NAD+ by Sephadex chromatography revealed that particles retained the stimulated state for at least 48 hours. Further addition of NAD+ to stimulated washed particles resulted in competitive inhibition of oxidase activity. Desensitization of the oxidase to the stimulatory effect of NAD+ was achieved by heating the particles at 50 degrees for 2 min without appreciable loss of enzymatic activity. Kinetic studies indicated that addition of NADH to electron transport particles prior to preincubation with NAD+ inhibited stimulation. In addition, NADH inhibited binding of [14C]NAD+. The utilization of artificial electron acceptors, which act as a shunt of the respiratory chain at or near the flavoprotein component, indicated that NAD+ acts as at the level of the NADH dehydrogenase at a site other than the catalytic one resulting in a conformational change which causes restoration as well as protection of oxidase activity.


Adverse events related to bystander naloxone administration in cases of suspected opioid overdose in British Columbia: An observational study.
Take-Home Naloxone programs have been introduced across North America in response to rising opioid overdose deaths. There is currently limited real-world data on bystander naloxone administration, overdose outcomes, and evidence related to adverse events following bystander naloxone administration. The research team used descriptive statistics from Take-Home Naloxone administration forms. We explored reported demographic variables and adverse events among people who received by-stander administered naloxone in a suspected opioid overdose event between August 31, 2012 and December 31, 2018 in British Columbia. We examined and contextualized differences across years given policy, program and drug toxicity changes. We used multivariate logistic regression to examine whether an association exists between number of ampoules of naloxone administered and the odds that the recipient will experience withdrawal symptoms. A large majority (98.1%) of individuals who were administered naloxone survived their overdose and 69.2% had no or only mild withdrawal symptoms. Receiving three (Adjusted Odds Ratio (AOR) 1.64 (95% Confidence Interval (CI): 1.08-2.48)) or four or more (AOR 2.19 (95% CI: 1.32-3.62)) ampoules of naloxone was significantly associated with odds of moderate or severe withdrawal compared to receiving one ampoule of naloxone. This study provides evidence from thousands of bystander reversed opioid overdoses using Take-Home Naloxone kits in British Columbia, and suggests bystander-administered naloxone is safe and effective for opioid overdose reversal. Data suggests an emphasis on titration during bystander naloxone training in situations where the person experiencing overdose can be adequately ventilated may help avoid severe withdrawal symptoms. We identified a decreasing trend in the likelihood of moderate or severe withdrawal over the study period.


Molecular manipulation using a tunnelling microscope.
In a very short time the scanning tunnelling microscope has become an important tool in surface science, and physics in general. Its primary use has been to obtain atomic-resolution images of surfaces, but recently, efforts have been made to use it to manipulate materials as well as image them. One may now reasonably ask if it is possible to move and alter matter predictably on an atomic scale. Here we report the accomplishment of the smallest yet, purposeful, spatially localized changes in matter, effected on a graphite surface. We believe that the changes result from the pinning of individual organic molecules to the graphite. The reverse manipulation, the removal of pinned molecules, has also been demonstrated. Finally, we have evidence that we can remove a portion of a pinned molecule, effectively performing transformations on single molecules using the tunnelling microscope.


Designing fluorinated cinchona alkaloids for enantioselective catalysis: controlling internal rotation by a fluorine-ammonium ion gauche effect (φ(NCCF)).
The C9 position of cinchona alkaloids functions as a molecular hinge, with internal rotations around the C8-C9 (τ(1)) and C9-C4' (τ(2)) bonds giving rise to four low energy conformers (1; anti-closed, anti-open, syn-closed, and syn-open). By substituting the C9 carbinol centre by a configurationally defined fluorine substituent, a fluorine-ammonium ion gauche effect (σ(C-H) → σ(C-F)*; F(δ-)⋅⋅⋅N(+)) encodes for two out of the four possible conformers (2). This constitutes a partial solution to the long-standing problem of governing internal rotations in cinchonium-based catalysts relying solely on a fluorine conformational effect.


Stochastic Petri net modeling of wave sequences in cardiac arrhythmias.
We describe a methodology for modeling heart rhythms observed in electrocardiograms. In particular, we present a procedure to derive simple dynamic models that capture the cardiac mechanisms which control the particular timing sequences of P and R waves characteristic of different arrhythmias. By treating the cardiac electrophysiology at an aggregate level, simple network models of the wave generating system under a variety of diseased conditions can be developed. These network models are then systematically converted to stochastic Petri nets which offer a compact mathematical framework to express the dynamics and statistical variability of the wave generating mechanisms. Models of several arrhythmias are included in order to illustrate the methodology.


Interactive registration between supine and prone scans in computed tomography colonography using band-height images.
In computed tomographic colonography (CTC), a patient is commonly scanned twice including supine and prone scans to improve the sensitivity of polyp detection. Typically, a radiologist must manually match the corresponding areas in the supine and prone CT scans, which is a difficult and time-consuming task, even for experienced scan readers. In this paper, we propose a method of supine-prone registration utilizing band-height images, which are directly constructed from the CT scans using a ray-casting algorithm containing neighboring shape information. In our method, we first identify anatomical feature points and establish initial correspondences using local extreme points on centerlines. We then correct correspondences using band-height images that contain neighboring shape information. We use geometrical and image-based information to match positions between the supine and prone centerlines. Finally, our algorithm searches the correspondence of user input points using the matched anatomical feature point pairs as key points and band-height images. The proposed method achieved accurate matching and relatively faster processing time than other previously proposed methods. The mean error of the matching between the supine and prone points for uniformly sampled positions was 18.41±22.07mm in 20 CTC datasets. The average pre-processing time was 62.9±8.6s, and the interactive matching was performed in nearly real-time. Our supine-prone registration method is expected to be helpful for the accurate and fast diagnosis of polyps.


Prognostic Significance of Pretreatment Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, or Monocyte-to-Lymphocyte Ratio in Endometrial Neoplasms: A Systematic Review and Meta-analysis.
Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), or monocyte-lymphocyte ratio (MLR) has been shown to be related to the poor prognosis of cervical cancer, ovarian cancer, breast cancer, and other malignant tumors, but their role in predicting the prognosis of endometrial cancer is still controversial. Therefore, we conducted this meta-analysis to evaluate the effectiveness of NLR more accurately, PLR, or MLR in predicting the prognosis of endometrial cancer (EC). This review systematically searched for relevant publications in databases of the Cochrane Library, PubMed, EMBASE, CNKI, WanFang, VIP, and CBM. Pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were determined and used to explore the association between inflammatory biomarkers (NLR, PLR, and MLR) and overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) in a random-effects model. We also conducted subgroup analysis and publication bias in this meta-analysis. Stata 12.0 was used for statistical analysis. This meta-analysis contained 14 eligible studies including 5,274 patients. Our results showed that NLR or PLR was associated with OS [NLR: HR, 2.51; 95% CI, 1.70-3.71; p <0.001 in univariate analysis (Ua); HR, 1.87; 95% CI, 1.34-2.60; p <0.001 in multivariate analysis (Ma); PLR: HR, 2.50; 95% CI, 1.82-3.43; p <0.001 in Ua; HR, 1.86; 95% CI, 1.22-2.83; p = 0.004 in Ma], but MLR was not associated with OS (HR, 1.44; 95% CI, 0.70-2.95; p = 0.325 in Ua; HR, 1.01; 95% CI, 0.39-2.60; p =0.987 in Ma). A further subgroup analysis found that the correlations were not affected by race, cutoff value, sample size, or treatment. Our meta-analysis showed that NLR or PLR was associated with DFS (NLR: HR, 2.50; 95% CI, 1.38-4.56; p =0.003 in Ua; HR, 2.06; 95% CI, 1.26-3.37, P =0.004 in Ma; PLR: HR, 1.91; 95% CI, 1.30-2.81; p = 0.001 in Ua), and NLR was associated with PFS only in the univariate analysis (HR, 1.71; 95% CI, 1.04-2.81; p =0.035 in Ua; HR, 1.79; 95% CI, 0.65-4.89; P =0.257 in Ma), but MLR was not associated with DFS (HR, 0.36; 95% CI, 0.03-4.13; p =0.409 in Ua). Our results indicated that pretreatment NLR and PLR were biomarkers of poor prognosis in patients with endometrial cancer. The results indicated that NLR or PLR was associated with OS and disease-free survival DFS, and NLR was associated with PFS only in univariate analysis, but MLR was not associated with OS or DFS.


[Therapy of cognitive deficits in schizophrenia with acetylcholinesterase inhibitors. A systematic overview].
Patients with schizophrenia suffer from cognitive deficits which are important predictors of functional outcome. Alterations such as reduced muscarinic and nicotinic receptors in the central cholinergic system in patients with schizophrenia may contribute to these cognitive impairments. Because such deficits do not respond to neuroleptic treatment, different approaches have been developed regarding pharmacological treatments that enhance central cholinergic transmission, e.g. with acetylcholinesterase inhibitors. In this review the pathophysiology of cognitive impairment in schizophrenia, results of studies using acetylcholinesterase inhibitors (donepezil, rivastigmine, physostigmine, and galantamine), and future research strategies are presented. Till now randomized, placebo-controlled studies exist only for donepezil and rivastigmine, and none could replicate the positive results of previous trials with open designs. More trials with higher numbers of patients are needed, particularly for substances with more complex mechanisms of action (e.g. galantamine).


Inclusion of LGBTQ persons in research related to pregnancy risk: a cognitive interview study.
Recently, researchers have begun considering whether and how to include lesbian, gay, bisexual, transgender and queer (LGBTQ) people in research about abortion and contraception care. Including LGBTQ people in research about abortion and contraception care, as well as the risk for unintended pregnancy more broadly, requires accurate assessment of risk for unintended pregnancy, which involves different considerations for LGBTQ people. We created a survey with existing sexual orientation and gender identity measures, new reproductive anatomy questions to guide skip patterns, gender neutral terminology in sexual and behavioural risk questions, and existing contraception and pregnancy intentions questions that were modified to be gender neutral. We then assessed the appropriateness of these measures through cognitive interviews with 39 individuals aged 18-44 years who were assigned female at birth and identified as LGBTQ. Participants were recruited in the San Francisco Bay Area of California, Baltimore, Maryland and other cities. Existing demographic questions on sexual orientation and gender identity were well received by participants and validating of participant reported identities. Participants responded positively to new reproductive anatomy questions and to gender neutral terminology in sexual behaviour and pregnancy risk questions. They felt skip patterns appropriately removed them out of inappropriate items (eg, use of contraception to avoid unintended pregnancy); there was some question about whether pregnancy intention measures were widely appropriate or should be further restricted. This study provides guidance on ways to appropriately evaluate inclusion of LGBTQ people in abortion and contraception research.


A phase I pharmacological and biological study of PI-88 and docetaxel in patients with advanced malignancies.
This study evaluated the safety, toxicity, pharmacological properties and biological activity of PI-88, a heparanase endoglycosidase enzyme inhibitor, with fixed weekly docetaxel in patients with advanced solid malignancies. This was a phase I study to determine the maximal-tolerated dose of escalating doses of PI-88 administered subcutaneously for 4 days per week, along with docetaxel 30 mg/m(2) given on days 1, 8, 15 of a 28-day schedule. Sixteen patients received a total of 42 courses of therapy. No dose-limiting toxicities were observed despite escalation to the highest planned dose level of PI-88 (250 mg/day). Frequent minor toxicities included fatigue (38%), dysgeusia (28.5%), thrombocytopenia (12%), diarrhea (14%), nausea (12%), and emesis (10%) in the 42 courses. No significant bleeding complications were observed. One patient developed a positive anti-heparin antibody test/serotonin releasing assay with positive anti-platelet factor 4/PI-88 antibodies and grade 1 thrombocytopenia in cycle 5, and was withdrawn from the study without any sequelae. PI-88 plasma concentrations (mirrored by APTT) and urinary elimination were linear and dose-proportional. Docetaxel did not alter the pharmacokinetic (PK) profile of PI-88, nor did PI-88 affect docetaxel PK. No significant relationship was determined between plasma or urine FGF-2, or plasma VEGF levels and PI-88 dose/response. Although no objective responses were observed; 9 of the 15 evaluable patients had stable disease for greater than two cycles of therapy. PI-88 administered at 250 mg/day for 4 days each week for 3 weeks with docetaxel 30 mg/m(2) on days 1, 8 and 15, every 28 days, was determined to be the recommended dose level for phase II evaluation. This combination was well tolerated without severe toxicities or PK interactions.


Association between maternal HIV infection and low birth weight and prematurity: a meta-analysis of cohort studies.
To assess the association between maternal human immunodeficiency virus (HIV) infection and low birth weight (LBW)/prematurity (PTD), we conducted a meta-analysis of cohort studies of HIV infected and uninfected women. Several English and Chinese databases were searched (updated to May 2015) to find the studies reporting infant outcomes associated with exposure to maternal HIV infection during pregnancy. Relevant articles were manually selected based on several inclusion and exclusion criteria. Fifty-two cohort studies including 15,538 (for LBW) and 200,896 (for PTD) HIV infected women met the inclusion criteria. There was significant heterogeneity among studies for maternal HIV infection associated with LBW/PTD (I(2) = 71.7%, P < 0.05, and I(2) = 51.8%, P < 0.05 for LBW and PTD, respectively). The meta-analysis demonstrated that the maternal HIV infection was significantly associated with both LBW (pooled odds ratio (OR): 1.73, 95% confidence interval (CI): 1.64, 1.82, P < 0.001) and PTD (pooled OR: 1.56, 95% CI: 1.49, 1.63, P < 0.001). No significant difference in the relationship between maternal HIV infection and adverse pregnancy outcomes was detected among the groups of different study periods. HIV infected women were at slightly higher risk of LBW in developing countries compared with women in developed countries (OR: 2.12 (95% CI: 1.81, 2.48) vs. 1.75 (95% CI: 1.44, 2.12)). Antiretroviral drugs usage did not significantly change the associations of maternal HIV exposure with LBW and PTD. HIV infected women were at higher risk of having a low birth weight infant or a preterm delivery infant compared with uninfected women. Such associations did not change significantly over time or were not significantly affected by the usage of antiretroviral drugs.


Histopathological parameters of Helicobacter pylori-associated gastritis in children and adolescents: comparison with findings in adults.
The pathohistological features of Helicobacter pylori-associated gastritis in children and adolescents are less well understood than they are in adults. The aim of the study was to compare histological parameters of H. pylori-infected children with those of adults. The retrospective study compared histological features of 111 children (mean age 10.8 +/- 3.8). Three paediatric age groups were analysed and the findings were compared with those of 111 adults (mean age 64.2 +/- 12.1). Degree of chronicity and activity of inflammation, mucus depletion and regeneration of foveolar epithelium by regenerating epithelium and H. pylori colonization were scored in antral biopsies. The histological parameters in children, i.e. degree of chronicity, activity of gastritis and the summed gastritis score, were not significantly different compared to those in adults. Replacement of foveolar epithelium by regenerating epithelium was significantly larger in adults compared to that of paediatric patients. The rate of low-grade mucus depletion and of the strongest degree of H. pylori colonization was higher in children than in adults. Children with antral nodularity had significantly higher histological score values. The histological differences between paediatric patients and adults are focused on signs of chronic inflammation and regeneration. Our results imply that antral nodularity is an important sign of highest-grade gastritis, especially in young children.


Effects of fluorescent dissolved organic matters (FDOMs) on perfluoroalkyl acids (PFAAs) in lake and river water.
This study presents the effects of fluorescent dissolved organic matters (FDOM) on perfluoroalkyl acids (PFAAs) in western Lake Chaohu and its inflow rivers. The surface water samples from the 27 sites in western Lake Chaohu and its inflow rivers were collected in March and September 2013. The contents of PFAAs and the FDOM in the water samples were measured by a high-performance liquid chromatograph - mass spectrometer (HPLC-MS) and by a fluorescence spectrophotometer, respectively. The temporal-spatial distributions of PFAAs and FDOM, as well as their interrelationships, were investigated. Eleven PFAA components were detected, and the mean concentration of total PFAAs (TPFAAs) in western Lake Chaohu and its inflow rivers were 12.93 ± 5.19 ng/L and 11.84 ± 9.50 ng/L, respectively. PFOA was the predominant contaminant in two regions (7.13 ± 3.07 ng/L and 4.30 ± 2.14 ng/L) followed by PFHxA (1.72 ± 0.80 ng/L and 1.42 ± 1.41 ng/L) and PFBA (1.44 ± 0.78 ng/L and 1.37 ± 0.78 ng/L). The mean concentration of total FDOM in western Lake Chaohu and its inflow rivers were 220.0 ± 40.30 μg quinine sulfate units (Q.S.)/L and 406.3 ± 213.1 μg Q.S./L, respectively. The significant, positive correlations were observed between the PFAAs and FDOMs in both the lake area and the inflow rivers. However, no significant correlation was observed between PFAAs and the dissolved organic carbon (DOC) in the lake area. This finding indicated that the residues and distributions of PFAAs were significantly dependent on the compositions of dissolved organic matters (DOM) and not on the total content of DOM.


[Neurological manifestations of ATTR amyloidosis].
Transthyretin amyloidosis (ATTR) is a rare disease in which the protein transthyretin (TTR) is deposited in the form of amyloid fibrils in various tissues and organs and secondarily leads to functional impairment, especially in peripheral nerves and the heart. A differentiation is made between hereditary and sporadic forms. The hereditary variant is inherited in an autosomal dominant manner and usually occurs in the younger to middle-aged, while the sporadic form occurs in older age and has no known genetic cause. Typical signs of hereditary ATTR amyloidosis (ATTRv, v for variant) include a rapidly progressing sensorimotor and autonomic polyneuropathy (PNP), cardiac dysfunction as well as ocular and gastrointestinal symptoms. A carpal tunnel syndrome often precedes the manifestation. Various options (tafamidis, patisiran, inotersen or vutrisiran) are available for the treatment of patients with ATTRv with PNP in Germany, depending on the severity. In the sporadic variant of wild-type ATTR amyloidosis (ATTRwt), symptoms of progressive cardiomyopathy are usually prominent; however, neurological assessment of these patients often also reveals a concomitant sensory ataxic PNP. The tetramer stabilizer tafamidis can be used for treatment. Because of this complex presentation, the management of patients with ATTR amyloidosis should be performed in interdisciplinary centers specialized in amyloidosis.


The impact of temporary artery occlusion during intracranial aneurysm surgery on long-term clinical outcome: Part II. The patient who undergoes elective clipping.
Temporary artery occlusion (TAO) during intracranial aneurysm surgery is a key element in facilitating aneurysm dissection and clipping. Despite its significance, knowledge of its effects on long-term clinical outcome in patients undergoing elective clipping for unruptured aneurysms is limited. This study evaluated the safety of this technique in this patient population by 1 surgeon. Patients managed for an intracranial aneurysm were followed from 2000-2009. This study included a cohort of patients found to have unruptured intracranial aneurysms who underwent TAO during their elective clipping procedure. Potential risk factors to affect outcome were considered. Effects of TAO on long-term clinical outcome were evaluated using the Glasgow Outcome Scale (GOS) obtained retrospectively by analyzing medical records at the last follow-up visit or discharge. Analyses included descriptive statistics, binary logistic regression, and ordinal logistic regression. Inclusion criteria were met by 246 patients (75.2% female, age 54 years±10.9) with electively clipped, unruptured aneurysms. Mean follow-up was 53 months±67.5. Mean temporary artery clipping time was 16.1 minutes±14.7. Of patients, 86% had a good outcome and made a complete recovery at last follow-up (GOS 5); 9% of patients were moderately disabled (GOS 4); 5% of patients were severely disabled (GOS 3), were in a vegetative state (GOS 2), or had died (GOS 1). TAO time had no effects on overall long-term clinical outcomes (P=0.59). Although patients with posterior circulation aneurysms had a worse outcome compared with patients with anterior circulation aneurysms (P=0.008), age (P=0.176) and aneurysm size (P=0.497) were not significantly associated with clinical outcome. This study did not demonstrate any relationship between limited duration of TAO and clinical outcome. Posterior circulation aneurysms are associated with worse long-term clinical outcomes in patients with electively clipped, unruptured aneurysms.


Bleeding risk in female patients undergoing intravesical injection of onabotulinumtoxinA for overactive bladder: a Danish retrospective cohort study.
We aimed to examine the risk of bleeding in female patients undergoing intravesical onabotulinumtoxinA (BTX-A) treatments and provide clinical recommendations for the perioperative management of patients on antithrombotic therapy prior to BTX-A treatments. This was a retrospective cohort of Danish female patients, who had their first BTX-A treatment because of an overactive bladder at the Department of Gynecology and Obstetrics, Herlev and Gentofte University Hospital, between January 2015 and December 2020. Data extraction was from an electronic medical journal system. BTX-A, Botox® Allergan was injected in the detrusor at 10-20 sites. Significant bleeding during or after a BTX-A treatment was defined as persistent macroscopic hematuria. Bleeding reporting was based on information obtained from journal notes. We included 400 female patients, who had a total of 1,059 BTX-A treatments. Median age at first BTX-A treatment was 70 years (IQR 21), and median number of BTX-A treatments was 2 (range 1-11). In total, 27.8% (n=111) received antithrombotic therapy. Within this group, 30.6% and 69.4% were on anticoagulant and antiplatelet therapy. No cases of hematuria were reported in our cohort. We found that no patients stopped their antithrombotic therapy, were bridged, or monitored by International Normalized Ration (INR) levels. We suggest that BTX-A treatments might be classified as low-risk procedures. Discontinuation of antithrombotic therapy is not required in the perioperative management of this patient group.


Compliance and Adherence to Enteral Nutrition Treatment in Adults: A Systematic Review.
To review the scientific literature that has verified and/or assessed compliance and adherence to enteral nutrition (EN) in adult patients. This study involved a critical analysis of articles retrieved from MEDLINE (PubMed), The Cochrane Library, Embase, Scopus and Web of Science using the terms "Treatment Adherence and Compliance" and "Enteral Nutrition", applying the filters "Comparative Study" or "Clinical Trial", "Humans" and "Adults". Date of the search: 25 October 2018. A total of 512 references were retrieved, of which 23 documents were selected after applying the inclusion and exclusion criteria. The techniques measuring adherence to EN were determined by dietary intake, self-reporting, counts of leftover containers or presence of complications; however, in no case were validated questionnaires used. The time and periodicity of the assessment presented very heterogeneous results, with measurement predominantly being done at the beginning and at the end of the study. The best adherence rates were obtained in hospitalized patients (approximately 80%). Frequent and regular monitoring of the adherence of patients under prolonged treatment with EN is necessary, and the use of measurement techniques that allow obtaining information on the causes of non-adherence facilitates early interventions to optimize treatment outcomes. Patient and/or caregiver education in the management of EN and the intervention of the community pharmacy in monitoring patients can be key to improving the adherence to EN.


Effect of oxotremorine on the acquisition of a conditioned avoidance response is modified by the estrous cycle, ovariectomy, and estradiol replacement in rats.
This study was designed to evaluate the influence of the hormonal status of the rat on the effects of a potent reversible muscarinic agonist, oxotremorine, on the acquisition of conditioning avoidance responses (CARs) and the performance of some spontaneous motor behaviors. Oxotremorine (OXO 50 and 100 micrograms/kg, intraperitoneally) given 5 min before testing improved active conditioned avoidance in intact female rats at estrus and in ovariectomized rats after estradiol replacement, and impaired performance in female rats at diestrus and after ovariectomy without estradiol replacement. No significant differences due to hormonal status of the rat in some spontaneous motor behaviors were observed. In fact, OXO in this dose range failed to induce significant changes in spontaneous motor activity, the number of rears diminished, and the time spent in grooming behavior increased in all groups studied. These results provided behavioral evidence for the hypothesis that central cholinergic activity is function of the hormonal status of the animal. Relationships between ovarian hormones and cholinergic system are discussed.


Brain Neuroplasticity Related to Lateral Ankle Ligamentous Injuries: A Systematic Review.
Lateral ankle sprains are the most common ankle injuries in sports and have the highest recurrence rates. Almost half of the patients experiencing lateral ankle sprains develop chronic ankle instability. Patients with chronic ankle instability experience persistent ankle dysfunctions and detrimental long-term sequelae. Changes at the brain level are put forward to explain these undesirable consequences and high recurrence rates partially. However, an overview of possible brain adaptations related to lateral ankle sprains and chronic ankle instability is currently lacking. The primary purpose of this systematic review is to provide a comprehensive overview of the literature on structural and functional brain adaptations related to lateral ankle sprains and in patients with chronic ankle instability. PubMed, Web of Science, Scopus, Embase, EBSCO-SPORTDiscus and Cochrane Central Register of Controlled Trials were systematically searched until 14 December, 2022. Meta-analyses, systematic reviews and narrative reviews were excluded. Included studies investigated functional or structural brain adaptations in patients who experienced a lateral ankle sprain or with chronic ankle instability and who were at least 18 years of age. Lateral ankle sprains and chronic ankle instability were defined following the recommendation of the International Ankle Consortium. Three authors independently extracted the data. They extracted the authors' name, publication year, study design, inclusion criteria, participant characteristics, the sample size of the intervention and control groups, methods of neuroplasticity testing, as well as all means and standard deviations of primary and secondary neuroplasticity outcomes from each study. Data reported on copers were considered as part of the control group. The quality assessment tool for observational and cross-sectional studies was used for the risk of bias assessment. This study is registered on PROSPERO, number CRD42021281956. Twenty articles were included, of which only one investigated individuals who experienced a lateral ankle sprain. In all studies combined, 356 patients with chronic ankle instability, 10 who experienced a lateral ankle sprain and 46 copers were included. White matter microstructure changes in the cerebellum have been related to lateral ankle sprains. Fifteen studies reported functional brain adaptations in patients with chronic ankle instability, and five articles found structural brain outcomes. Alterations in the sensorimotor network (precentral gyrus and supplementary motor area, postcentral gyrus and middle frontal gyrus) and dorsal anterior cingulate cortex were mainly found in patients with chronic ankle instability. The included studies demonstrated structural and functional brain adaptations related to lateral ankle sprains and chronic ankle instability compared to healthy individuals or copers. These adaptations correlate with clinical outcomes (e.g. patients' self-reported function and different clinical assessments) and might contribute to the persisting dysfunctions, increased re-injury risk and long-term sequelae seen in these patients. Thus, rehabilitation programmes should integrate sensorimotor and motor control strategies to cope with neuroplasticity related to ligamentous ankle injuries.


Piagetian's principles on moral development and its influence on the oral hygiene practices of Indian children: An embedded mixed-method approach.
Moral principles in children can influence their oral hygiene practices and can be beneficial in providing better oral health care. To assess the consistency of Piaget's moral development principles in Indian children aged 7 to 11 years and evaluate its influence on their oral hygiene practices. The first phase of the embedded mixed-method approach included telephone interviews of 50 children on eight situations of moral development as suggested by Jean Piaget. Children were categorised into heteronomous and autonomous moralities based on the content analysis. The second phase of the study included a semi-structured qualitative interview on knowledge and practice behaviour of children on oral hygiene maintenance. There was no significant difference in the overall moral development of children aged 7 to 9 years and 9 to 11 years (p = .57). Only 4.8% of girls had heteronomous morality, and a significant difference was noted between boys and girls (p = .014). There was a significant difference in the oral hygiene practices observed between heteronomous morality and autonomous morality children. Children were autonomous in their morality at 7 to 9 years of age. Children with autonomous morality performed better oral hygiene practices than children with heteronomous morality.


Effect of hydroxypropyl-beta-cyclodextrin on efficacy of oral itraconazole in disseminated murine cryptococcosis.
The therapeutic efficacy of itraconazole solubilized in either the commonly used vehicle, polyethylene-glycol-200 (PEG) or hydroxypropyl beta-cyclodextrin was compared in a murine model of disseminated cryptococcosis. Itraconazole at doses of up to 120 mg/kg/day solubilized in PEG were found not to be effective. However, itraconazole at doses > or = 30 mg/kg/day solubilized in hydroxypropyl-beta-cyclodextrin markedly prolonged survival and a relationship between dose and survival was seen.


Identification and isolation of the yeast cytochrome c gene.
The iso-1-cytochrome c gene of yeast has been identified and cloned using a synthetic oligodeoxynucleotide as a hybridization probe. The oligomer d[pT-T-A-G-C-A-G-A-A--C-C-G-G] is complementary to a region near the N terminal coding region of the yeast cyc 1 gene. Of several yeast Eco RI fragments which hybridize to this probe, one is changed in size by a G leads to T mutation which eliminates an Eco RI site within the cyc 1 gene. Both the wild-type and the RI- mutant forms were cloned in lambda gt vectors. Maxam-Gilbert sequencing for 91 nucleotides into the coding region for iso-1-cytochrome c yielded a DNA sequence in perfect correspondence with the known protein sequence.


Mycobacteria and macrophage activation.
Recent studies that challenged some older concepts have led to the following conclusions: 1) During an infection of mice with M. bovis, BCG macrophages are activated according to certain criteria, but the increase in their bactericidal or bacteriostatic activity is limited to a small number of bacteria species; 2) interferon-gamma can activate macrophages in vitro and in vivo, but these cells do not exhibit increased bactericidal activity; 3) a 65-kDa protein of mycobacteria can activate macrophages in vivo to a limited degree only; and 4) granulocytes stimulated with interferon-gamma kill ingested M. fortuitum more efficiently than normal granulocytes.


Gray-scale ultrasound detection of carotid body tumors. Report of 2 cases.
Ultrasonography may be useful as a screening test for carotid body tumors before arteriography. Such tumors are seen as solid, well-circumscribed, weakly echogenic masses located at the carotid bifurcation.


Preoperative human-telomerase reverse transcriptase mRNA in peripheral blood and tumor recurrence in living-related liver transplantation for hepatocellular carcinoma.
In this study we evaluated the potential role of preoperative h-TERT mRNA expression in peripheral blood as a tool for predicting prognosis and tumor recurrence after living-related liver donor transplantation (LRLDT). The study included patients with unresectable HCC who underwent LRLDT from July 1999 to May 2003. There was no significant difference between the survival curves of those patients who met the Milan criteria and those who did not. However, there was a statistically significant difference (p=0.032) between the survival curves of those patients with positive preoperative h-TERT mRNA expression, and those who either had an initially negative preoperative h-TERT mRNA or who converted from positive to negative after neoadjuvant immunochemotherapy. In conclusion, the presence or absence of h-TERT mRNA in the peripheral blood may be a useful criterion in evaluating HCC patients for transplantation, as well as a valuable method of assessing anti-tumor therapy and tumor relapse.


Comparative study of laparoscopic versus open technique for simultaneous resection of colorectal cancer and liver metastases with propensity score analysis.
Laparoscopic liver resection for metastatic colorectal cancer (CRC) remains controversial. The objective of this study was to compare the short-term and mid-term outcomes of patients with CRC undergoing laparoscopic versus open colorectal resection with simultaneous resection for liver metastases. A total of 126 patients underwent combined laparoscopic resection of CRC and synchronous colorectal liver metastases between 2008 and 2016. A total of 318 patients were treated by an open approach during the above period. By propensity score matching, 109 patients who underwent laparoscopic resection and 109 patients who had an open approach were compared. Analyzed variables included patient characteristics, tumor features, and short-term and mid-term outcomes. Demographic features and pathologic outcomes were similar in both groups after propensity score matching. Three (2.8%) patients undergoing laparoscopic liver resection experienced conversion to open procedure. There was no difference in hospital stay (p = 0.078), transfusion rate (p = 0.686), or time of bowel function return (p = 0.570) between the two groups. The laparoscopic group and the open approach group also showed similar 3-year overall survival rate (74.4% vs. 79.1%; p = 0.792) and 3-year disease-free survival rate (58.5% vs. 55.2%; p = 0.391). However, postoperative morbidity rate was significantly lower in the laparoscopic group (20.2% vs. 33.0%; p = 0.032). Laparoscopic colorectal resection with simultaneous resection of liver metastases showed satisfactory oncologic outcomes with some short-term advantages compared to the open approach. Thus, laparoscopic approach could be a good alternative of open approach for simultaneous liver and colon resection in patients with CRC.


Microdissection-An Essential Prerequisite for Spatial Cancer Omics.
The problem with cancer tissue is that its intratumoral heterogeneity and its complexity is extremely high as cells possess, depending on their location and function, different mutations, different mRNA expression and the highest intricacy in the protein pattern. Prior to genomic and proteomic analyses, it is therefore indispensable to identify the exact part of the tissue or even the exact cell. Laser-based microdissection is a tried and tested technique able to produce pure and well-defined cell material for further analysis with proteomic and genomic techniques. It sheds light on the heterogeneity of cancer or other complex diseases and enables the identification of biomarkers. This review aims to raise awareness for the reconsideration of laser-based microdissection and seeks to present current state-of-the-art combinations with omic techniques.


Typicality mediates performance during category verification in both ad-hoc and well-defined categories.
The typicality effect is present in neurologically intact populations for natural, ad-hoc, and well-defined categories. Although sparse, there is evidence of typicality effects in persons with chronic stroke aphasia for natural and ad-hoc categories. However, it is unknown exactly what influences the typicality effect in this population. The present study explores the possible contributors to the typicality effect in persons with aphasia by analyzing and comparing data from both normal and language-disordered populations, from persons with aphasia with more semantic impairment versus those with less semantic impairment, and from two types of categories with very different boundary structure (ad-hoc vs. well-defined). A total of 40 neurologically healthy adults (20 older, 20 younger) and 35 persons with aphasia (20 LSI (less-semantically impaired) patients, 15 MSI (more-semantically impaired) patients) participated in the study. Participants completed one of two tasks: either category verification for ad-hoc categories or category verification for well-defined categories. Neurologically healthy participants showed typicality effects for both ad-hoc and well-defined categories. MSI patients showed a typicality effect for well-defined categories, but not for ad-hoc categories, whereas LSI patients showed a typicality effect for ad-hoc categories, but not for well-defined categories. These results suggest that the degree of semantic impairment mediates the typicality effect in persons with aphasia depending on the structure of the category. After reading this article, the reader should be able to: (1) Describe the typicality effect and in which populations it occurs. (2) Explain how the typicality effect might change depending on category structure. (3) summarize how semantic impairment influences category representation and/or access.


Synthetic peptides derived from the sequence around the plasmin cleavage site in vitronectin. Use in mapping the PAI-1 binding site.
A series of 8 peptides derived from the amino acid sequence accommodating the plasmin cleavage site in vitronectin were synthesized and used to map its binding site for the type I plasminogen activator inhibitor (PAI-1). This mapping assigned the inhibitor binding site to the K348-R370 region with high affinity recognition elements within the K348-R357 sequence. These results account for our previous finding that cleavage of the R361-S362 bond by plasmin significantly reduces the affinity between PAI-1 and vitronectin, since it splits the PAI-1 binding site in two. Furthermore, in the case of the two-chain form of vitronectin, this cleavage detaches the S362-R379 peptide which provides some of the affinity elements for the binding of PAI-1.


Intact spore MALDI-TOF mass spectrometry and proteomic analysis of Puccinia pathogenic fungi.
The aim of this work was to develop a method for the identification of pathogens causing rust diseases of crops using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) of intact cells or spores (IC/IS). All optimizations were performed with Puccinia triticina, the causal agent of wheat leaf rust. Experiments included selection of washing solvents for spores, finding of an optimal concentration of spores in suspension and the most suitable matrix system as well as an evaluation of different sample preparation techniques. The best results were obtained when the spores were washed with acetonitrile/0.1% (v/v) trifluoroacetic acid, 7:3, v/v. A mixture of ferulic and sinapinic acids (5:15mgml(-1)) dissolved in acetonitrile/2.5% (v/v) trifluoroacetic acid, 7:3, v/v, was found optimal for the deposition of samples (50μg spores per μl) by two-layer volume technique. The optimized protocol was subsequently applied to other Puccinia species (Puccinia graminis, Puccinia striiformis and Puccinia coronata). Together with the use of the software BIOSPEAN, not only different species but also various pathotypes of the same species, which differ in their virulence, could be discriminated. There were 108 and 29 proteins identified from P. striiformis and P. graminis spores, respectively, after an acidic extraction in the matrix solvent mimicking the sample preparation for MALDI. Besides the presence of ribosomal proteins, histones, regulatory proteins and enzymes, also extracellular proteins participating in the pathogenesis were found. Finally, for both species, several proteins were assigned to signals in typical mass spectrometric profiles and suggested as diagnostic markers.


Investigating the self-study phase of an inverted biochemistry classroom - collaborative dyadic learning makes the difference.
The inverted classroom approach is characterized by a primary self-study phase for students followed by an on-site, face-to-face teaching phase that is used to deepen the prior acquired knowledge. Obviously, this teaching approach relies on the students preparing before the on-site phase, which in turn requires optimized preparatory material as well as defined working instructions. The major aim of this study, therefore, was to investigate the effect of different preparatory materials and working instructions for the self-study phase of an e-learning-based inverted classroom on the knowledge gained by medical students in biochemistry. Furthermore, we analyzed whether collaborative dyadic learning during the self-study phase is more effective than individual learning with respect to knowledge gain. The study was performed in a biochemistry seminar for second semester medical students at Ulm University in Germany. This seminar was held using an e-learning-based inverted classroom. A total of 196 students were divided into three homogeneous study groups that differed in terms of the working material and instructions provided for the self-study phase. Knowledge gain was measured by formative tests at the beginning of the on-site phases. Questionnaires were also handed out asking about motivation, interest and learning time in the self-study phases. Students who were told to prepare in collaborating dyads during the self-study phase performed better in formative tests taken at the beginning of on-site phases than learners who were told to prepare individually. The study material that was provided was of minor importance for the differences in formative testing since almost all students prepared for the on-site phases. With the dyadic learning approach, both students benefited from this collaboration, characterized by a higher motivation and interest in the topic, as well as a longer time spent on task. Our study provides strong evidence that the study material, but more importantly the instructions provided for the self-study phase, affect students` knowledge gain in an e-learning-based inverted classroom. The instructed collaboratively working group was the most successful.


Progressive pulmonary paracoccidioidomycosis a study of 34 cases observed in Rio Grande do Sul (Brazil).
Data on 34 patients with progressive pulmonary paracoccidioi domycosis seen in the State of Rio Grande do Sul (Brazil) are reviewed. Clinical manifestations were similar to those of a prolonged or a recurrent undifferentiated respiratory infection. Roentgenographic findings were also non-characteristic. A mycologic diagnosis was readily made when sputum was available.


Effects of recombinant human AMH on SCF expression in human granulosa cells.
The aim of the present study was to investigate the effects of recombinant human anti-mullerian hormone (rhAMH) on Stem Cell Factor (SCF) expression in human granulosa cells (GCs). GCs were obtained from infertile patients undergoing IVF-ET cycles and cultured with 20 ng/ml of rhAMH. The levels of SCF mRNA and protein were detected in both matched and experimental group by real-time PCR, immunofluorescence, and ELISA, respectively, on day 4 of culture. We found that human GCs expressed SCF mRNA and protein, and SCF expression in the experimental group was significantly lower than that in the matched group (p < 0.05). We further showed that rhAMH inhibited SCF expression at mRNA and protein levels.


Tet Enzymes-Mediated DNA 5hmC Modification in Cerebral Ischemic and Hemorrhagic Injury.
5-Hydroxymethylcytosine (5hmC) has recently been found that plays an important role in many diseases; however, there are still few studies in the field of stroke. The purpose of this review is to introduce the influence and function of 5hmC in stroke, in order for more people can study it. In this review, we introduced the role of 5hmC in ischemia and hemorrhage stroke, and summarized the possible therapeutic prospects of 5hmC in stroke. In conclusion, we suggest that 5hmC may serve as a biomarker or therapeutic target for the treatment of stroke.


Bone marrow space volume of the mandible influencing intraoperative blood loss in bilateral sagittal split osteotomy: A pilot Study.
The aim of this study was to investigate whether the bone marrow space volume of the mandible affects blood loss during bilateral sagittal split osteotomy (BSSO). Sixteen patients who underwent BSSO in our hospital were included in this study. Bone marrow space volume of the mandible was measured by analyzing images from computed tomography. Blood loss during BSSO was measured by weighing gauze, measuring suctioned blood, and adjusting for the volume of irrigation solution used during BSSO. Mean blood loss during BSSO for the 16 patients was 200.5 ml, and patients were divided into: Group I, with less than mean blood loss; and Group II, with greater than mean blood loss. Total bone marrow space volume was significantly greater in Group II (12,450.7 ± 2644.3 mm3) than in Group I (9130.3 ± 3005.8 mm3; P<0.05). A correlation between bone marrow space volume and blood loss during BSSO was suggested, and these results are beneficial for surgeons planning and preparing the orthognathic surgery.


Sometimes it takes darkness to see the light: pitfalls in the interpretation of cell proliferation markers (Ki-67 and PCNA).
The degree of cell proliferation in a tumor is often associated with metastatic risk and mortality. Proliferating cell nuclear antigen (PCNA) and Ki-67 are proliferation markers that can be used to assess malignant potential in cutaneous lesions and pathological cell proliferation in psoriasis. These markers are elevated during periods of cell proliferation; however, they are also upregulated following UV irradiation. This upregulation may be problematic, as many skin lesions are subject to sun exposure in an everyday setting.


Effects of temperature on diphosphopyridine nucleotide-linked isocitrate dehydrogenase from bovine heart. Aspects of the kinetics, stability, and quarternary structure of the enzyme.
A temperature-dependent conformational change of the active DPN-linked isocitrate dehydrogenase was observed. When initial reaction kinetic data were examined between 35 and 5 degrees, the Hill number (n) varied from 2 at higher to n approaching unity at lower temperatures, with an inflection point at 17 degrees. The presence of manganous isocitrate in the incubation media shifted the transition temperature for enzyme inactivation by 5,5'-dithiobis(2-nitrobenzoate) from 8-16 degrees. These temperature-dependent transitions were paralleled by progressive changes in sedimentation velocities from s20, w of 10.4 at 25 degrees to 7.3 at 10 degrees as measured by active band centrifugation. The linear Arrhenius plot for apparent V max and the constancy of S0.5 for the substrate manganous isocitrate between 35 and 5 degrees suggest that this temperature-dependent conformational change may not be solely related to manganous isocitrate. Further indications of equilibria between different species of enzyme in solution and effects of substrates and cofactors on conformation came from studies of specific activity of enzyme diluted into buffers at 3 and 25 degrees. Dilution to concentrations between 10 and 25 mum enzyme resulted in relatively rapid protein concentration-dependent inactivation which could be prevented and fully reversed by manganous isocitrate. No further substantial inactivation was found subsequent to this phase at 25 degrees. Lowering the temperature of the dilution buffer to 3 degrees favored formation of enzyme species exhibiting a further time and pH-dependent loss of activity which became independent of protein concentration below 7 mum enzyme. The rate of cold inactivation was reduced by raising the ionic strength of the buffer and its progress could be arrested by manganous isocitrate; however, the substrate did not restore the original activity.


10-year practice-based evaluation of ceramic and direct composite veneers.
This 10-year practice-based study aimed to compare survival and success of direct resin composite and ceramic veneers placed in a private dental practice, between January 2008 and March 2014. Data were retrieved from a clinical practice's records and were anonymized typed into electronic files. All veneer information was recorded, including previous restorations, repairs or failures, materials used, dates, patient, and age. We analyzed 1459 veneer restorations, of which 1043 (71.5%) were direct composite, and 416 (28.5%) were ceramic, placed in 341 patients. The mean patients' age was 47.8 years, and the mean number of restorations per patient was 4.3 restorations. During all follow-up, 957 (65.6%) veneers were successful without any repair, 252 (17.3%) were repaired and still in place, and 250 (17.1%) had a failure that resulted in replacement. Replacements were usually carried out with the same material placed at first. Considering success analysis, annual failure rates (AFR) for veneers in 5 and 10 years were 9.1% and 10% for direct composite and 2.9% and 2.8% for ceramic, respectively. Survival analysis showed AFR of 3.9% and 4.1% for composite and 1.4% and 1.2% for ceramic at the same periods. Cox regression was made for both success and survival outcomes. Composite veneers presented a higher risk of failure than ceramic veneers with higher hazard ratios for survival (HR) [HR 4.00 (2.74-5.83)] and success [HR 5.16 (2.65-10.04)]. Ceramic veneers had superior longevity than direct composite veneers in both success and survival analysis.


Hyperfine structure resolved by 2 to 4 GHz EPR of cytochrome c oxidase.
Using low frequency 2 to 4 GHz EPR at 10 K, we have resolved previously unseen hyperfine structure associated with the EPR-detectable copper signal of cytochrome c oxidase. The observed hyperfine structure appears consistent with hyperfine coupling to copper; although to account for all of the observed structure, an additional magnetic interaction is required as well. This work points out the utility of the 2 to 4 GHz EPR technique for resolving electronic hyperfine structural information from copper and possibly other paramagnetic sites in biomolecules when random variation in electronic g values is a cause of EPR line-broadening.


Functional dissection of structural domains in the receptor for colony-stimulating factor-1.
Receptor tyrosine kinases (RTKs) transduce external signals to the interior of the cell via a cytoplasmic kinase domain. We demonstrated previously that ligand-induced kinase activation of the colony-stimulating factor-1 receptor (CSF-1R) occurs via receptor oligomerization without propagation of conformational changes through the transmembrane (TM) domain (Lee, A. W., and Nienhuis, A. W. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 7270-7274). We have now examined the role of the different subdomains in the metabolic and signaling properties of CSF-1R. Two types of chimeric receptors have been utilized, Glyfms A, with the extracellular and TM domains of glycophorin A (GpA) and the cytoplasmic domain of CSF-1R, and Glyfms B, where only the extracellular domain originates from GpA. Glyfms A was found to exhibit a higher basal level of in vitro kinase activity, an increased associated phosphatidylinositol (PtdIns) 3-kinase activity and to support enhanced cellular mitogenesis, compared with wild-type CSF-1R or to Glyfms B. The constitutive activation of Glyfms A is consistent with the hypothesis that the TM domain may play a role in receptor oligomerization. Cross-linking with anti-GpA antibodies activated the kinase function of Glyfms B leading to an increase in PtdIns 3-kinase association and to the transmission of a mitogenic signal. Our results indicate that an activated kinase domain contains the major determinant for coupling with PtdIns 3-kinase, independent of extracellular and TM sequences and of ligand binding. Both chimeric receptors underwent internalization in the presence of anti-GpA antibodies but were not degraded, including the tyrosine-phosphorylated and kinase-active population. These results suggest that structural determinants in the extracellular domain must be important for targeting internalized receptors for lysosomal degradation.


Simple and sensitive method for determination of glycoalkaloids in potato tubers by high-performance liquid chromatography with chemiluminescence detection.
A novel, simple and sensitive high-performance liquid chromatographic method for the determination of the potato glycoalkaloids, alpha-solanine and alpha-chaconine, based on the chemiluminescent reaction of tris(2,2'-bipyridine)ruthenium(III) has been developed. The calibration graph was linear in the range of 5 ng/ml-10 microg/ml for both alpha-solanine and alpha-chaconine. The detection limits of alpha-solanine and alpha-chaconine were 1.2 and 1.3 ng/ml, respectively. This method was successfully applied to a potato tuber sample without cleanup, pre-concentration, and derivatization steps. The recoveries (mean +/- standard deviation, %) of alpha-solanine and alpha-chaconine spiked in tuber pith at 10 microg/g (n = 6) were 101.0 +/- 4.4% and 103.6 +/- 7.1%, respectively.


Media conditioned by retinal pigment epithelial cells suppress the canonical Wnt pathway.
Retinal pigment epithelial (RPE) cells play critical roles in the maintenance of visual function, partly by secreting various biologically active factors that modulate the intraocular environment. Recent studies suggest involvement of Wnt proteins secreted by RPE cells in the pathogenesis of photoreceptor degeneration. In the present study, we examined, via the luciferase assay, the effect of media conditioned by RPE cells (RPE-CM) on activity of the canonical Wnt pathway in vitro. We isolated primary RPE cells from Long-Evans rats at P6-P9. In culture, these cells formed a monolayer with polygonal cell morphology and demonstrated repigmentation at confluency and immunoreactivity for ZO-1, a marker for tight junctions. To evaluate the effect of RPE-CM on the canonical Wnt pathway, we replaced the culture media of COS-7 cells transfected with (Tcf)(7)LUC, a multimeric Tcf-responsive element luciferase reporter construct, with RPE-CM and measured luciferase activity with or without Wnt3a or SB216763, a specific GSK3 inhibitor. RPE-CM did not enhance basal or Wnt3a-induced (Tcf)(7)LUC activity; instead, this activity decreased by 60%. RPE-CM also reduced SB216763-induced (Tcf)(7)LUC activity by 65%, which suggests that the inhibitory effect of RPE-CM is probably due to intracellular crosstalk rather than extracellular antagonism. RPE cells may thus be able to modulate the intraocular environment by regulating the canonical Wnt pathway.


Can rotational atherectomy cause thermal tissue damage? A study of the potential heating and thermal tissue effects of a rotational atherectomy device.
Thermal tissue damage (TTD) is customarily associated with some lasers. The thermal potential of rotational atherectomy (RA) devices is unknown. We investigated the temperature profile and potential TTD as well as the value of fluid flushing of an RA device. We used a high-resolution infrared imaging system that can detect changes as small as 0.1 degree C to measure the temperature changes at the tip of a fast RA device with and without fluid flushing. To assess TTD, segments of porcine aorta were subjected to the rotating tip under controlled conditions, stained by a special histochemical stain (picrisirius red) and examined under normal and polarized light microscopy. There was significant heating of the rotating cam. The mean "peak" temperature rise was 52.8 +/- 16.9 degrees C. This was related to rotational speed; thus the "peak" temperature rise was 88.3 +/- 12.6 degrees C at 80,000 rpm and 17.3 +/- 3.8 degrees C at 20,000 rpm (p < 0.001, t-test). Fluid flushing at 18 ml/min reduced, but did not abolish, heating of the device (11.8 +/- 2.9 degrees C). A crater was observed in all segments exposed to the rotating tip. The following features were most notable: (i) A zone of "thermal" tissue damage extended radially from the crater reaching adventitia in some sections, especially at high speeds. This zone showed markedly reduced or absent birefringence. (ii) Fluid flushing of the catheter reduced the above changes but increased the incidence and extent of dissections in the media, especially when combined with high atherectomy speeds. (iii) These changes were observed in five of six specimens exposed to RA without flushing, but in only one of six with flushing (p < 0.05). (iv) None of the above changes was seen in control segments. RA is capable of generating significant heat and potential TTD. Fluid flushing reduced heating and TTD. These findings warrant further studies in vivo, and may influence the design of atherectomy devices.


A self-improving triboelectric nanogenerator with improved charge density and increased charge accumulation speed.
Charge density is one of the most important parameters of triboelectric nanogenerators since it directly determines performance; unfortunately, it is largely restricted by the phenomenon of air breakdown. Here, we design a self-improving triboelectric nanogenerator with improved charge density. A maximum effective charge density of 490 μC m-2 is obtained, which is about two times higher than the highest reported charge density of a triboelectric nanogenerator that operates in an air environment. At the beginning of the working process, the charge accumulation speed is increased 5.8 times in comparison with a triboelectric nanogenerator that is incorporated into the self-improving device. The self-improving triboelectric nanogenerator overcomes the restriction of air breakdown and exhibits an increased effective charge density, which contributes to the improvement of the output performance, and the increase of charge accumulation speed will accelerate the increase of the output power at the start of operation.


Costs of alcohol and drug-involved crime.
A large proportion of violent and property crimes involve alcohol or other drugs (AOD). AOD use only causes some of these crimes. This paper estimates the costs of AOD-involved and AOD-attributable crimes. Crime counts are from government statistics adjusted for underreporting. The AOD-involved portion of crime costs is estimated from inmate surveys on alcohol and illicit drug use at the time of the crime. The costs and AOD-attributable portion of AOD-involved crimes come from published studies. They include tangible medical, mental health, property loss, future earnings, public services, adjudication, and sanctioning costs, as well as the value of pain and suffering. An estimated 5.4 million violent crimes and 8 million property crimes involved AOD use in 1999. Those AOD-involved crimes cost society over 6.5 billion dollars in medical and mental health care and almost 65 billion dollars in other tangible expenses (in 1999 dollars). If the value of pain, suffering, and lost quality of life is added, AOD-involved crime costs totaled 205 billion dollars. Violent crimes accounted for more than 85% of the costs. Roughly estimated, crimes attributable to alcohol cost 84 billion dollars, more than 2 times the 38 billion dollars attributable to drugs. Although American media--news and entertainment--dwell on the links between drugs and crime, alcohol-attributable crime costs are double drug-attributable ones. Effective efforts to reduce the abuse of alcohol and illicit drugs should reduce costs associated with crime.


Comparative analysis between centrifuged hematocrit and "point-of-care" hemoglobin: impact on erythropoietin dosing.
The purpose of this CQI project was to examine the degree of anemia among our dialysis population and compare centrifuged hematocrits (HCTs) with point-of-care HemoCue hemoglobin (HGB) for accuracy and to assess any differences in patient outcomes. It was concluded that the point-of-care HemoCue HGB was more accurate than the centrifuged HCT when compared to the laboratory method. It was further concluded that accurate weekly results facilitated more appropriate patient EPO dosages, which in turn influenced patient outcomes.


Inhibiting Pneumococcal Surface Antigen A (PsaA) with Small Molecules Discovered through Virtual Screening: Steps toward Validating a Potential Target for Streptococcus pneumoniae.
The pneumococcal surface antigen A (PsaA) metal transporter protein provides manganese to bacterial cells. The X-ray crystal structures of PsaA, in both closed (Mn bound) and open (metal free) conformations, were explored with virtual screening to identify potential inhibitors of manganese transport. We pursued three strategies for inhibition: i) targeting a cavity close to the bound Mn to keep the metal in place; ii) targeting the metal-free Mn site to prevent metal uptake; and iii) targeting a potentially druggable allosteric site involving loops that translate between the conformations. Tiered assays were used to test the resulting 170 acquired hits: i) assay 1 tested the compounds' growth inhibition of the TIGR4 S. pneumoniae strain (ΔPsaA mutant control), yielding 80 compounds (MIC≤250 μm); ii) assay 2 tested if the addition of 20 μm Mn to inhibited cell cultures restored growth, yielding 21 compounds; and iii) assay 3 confirmed that the restored bacterial growth was Mn concentration dependent, as was the restoration of ΔPsaA growth, yielding 12 compounds with MICs of 125 μm or greater. It may be possible for a small molecule to inhibit PsaA, but we have not yet identified a compound with exemplary properties.


K88 variants K88ab, K88ac and K88ad in oral vaccination of different porcine adhesive phenotypes. Immunological aspects.
Sows of different adhesive phenotypes were vaccinated orally during the last 4 weeks of gestation with K88-positive Escherichia coli. Sows susceptible to adhesion by the K88 variant of the vaccination strain produced a significant IgA-class specific anti-K88 response in colostrum and milk and post-farrowing serum. Indications for an IgM and IgG-class specific anti-K88 response were also found in this group but only in milk. In sows resistant to adhesion by the K88 variant of the vaccination strain only an IgA-class specific anti-K88 antibody response was found in mammary secretions and in post-farrowing sera, but titres did not reach the high values of the former group. The response in the second group was attributed to the frequent administration of large quantities of K88-positive E. coli which to some extent can be compared with a colonization effect. Specificity for the serological components of the K88 variants was detectable in colostral IgA of sows susceptible to the vaccination strain only.


Inhibitory effects of dietary flavonoids on purified hepatic NADH-cytochrome b5 reductase: structure-activity relationships.
The structure-activity relationships of flavonoids with regard to their inhibitory effects on NADH-cytochrome b5 reductase (E.C. 126.96.36.199), a clinically and toxicologically important enzyme, are not known. In the present study, the inhibitory effects of fourteen selected flavonoids of variable structure on the activity of purified bovine liver cytochrome b5 reductase, which shares a high degree of homology with the human counterpart, were investigated and the relationship between structure and inhibition was examined. Of all the compounds tested, the flavone luteolin was the most potent in inhibiting b5 reductase with an IC50 value of 0.11 μM, whereas naringenin, naringin and chrysin were inactive within the concentration range tested. Most of the remaining flavonoids (morin, quercetin, quercitrin, myricetin, luteolin-7-O-glucoside, (-)-epicatechin, and (+)-catechin) produced a considerable inhibition of enzyme activity with IC50 values ranging from 0.81 to 4.5 μM except apigenin (36 μM), rutin (57 μM) and (+)-taxifolin (IC50 not determined). The magnitude of inhibition was found to be closely related to the chemical structures of flavonoids. Analysis of structure-activity data revealed that flavonoids containing two hydroxyl groups in ring B and a carbonyl group at C-4 in combination with a double bond between C-2 and C-3 produced a much stronger inhibition, whereas substitution of a hydroxyl group at C-3 was associated with a less inhibitory effect. The physiologically relevant IC50 values for most of the flavonoids tested regarding b5 reductase inhibition indicate a potential for significant flavonoid-drug and/or flavonoid-xenobiotic interactions which may have important therapeutic and toxicological outcomes for certain drugs and/or xenobiotics.


Regulation of uncoupling protein activity in phosphorylating potato tuber mitochondria.
In isolated potato tuber mitochondria, palmitic acid (PA) can induce a H+ leak inhibited by GTP in the phosphorylating (state 3) respiration but not in the resting (state 4) respiration. The PA-induced H+ leak is constant when state 3 respiration is decreased by an inhibition of the succinate uptake with n-butyl malonate (nBM). We show that the efficiency of inhibition by GTP is decreased when state 3 respiration is progressively inhibited by antimycin A (AA) and is restored following subsequent addition of nBM. We propose that in phosphorylating potato tuber mitochondria, the redox state of ubiquinone, which can antagonistically be varied with AA and nBM, modulates inhibition of the PA-activated UCP-sustained H+ leak by GTP.


Infectious complications in renal transplant recipients.
Renal transplantation has become a well-established therapeutic option for end-stage renal disease, but infectious diseases remain a significant cause of morbidity and mortality. Although a wide variety of pathogens may cause infection, viral ones must be regarded as the single most important class of infections. Progress has been made both in the prevention and the early recognition treatment of infections that are closely linked to rejection. Immunosuppressive therapy is central to the pathogenesis of both. Because of the particular characteristics of transplant recipients, it is desirable to establish a close collaboration between nephrologists, surgeons, and infectious disease specialists for the management of these patients. In this article, we describe the different kinds of infectious disease that may affect patients with kidney transplant and the fundamental principles of clinical management, particularly our experience in Polyoma virus (BK) infection.


Cardiac β-adrenergic receptor activation mediates distinct and cell type-dependent changes in the expression and distribution of connexin 43.
Activation of the sympatho-β-adrenergic receptors (β-ARs) system is a hallmark of heart failure, leading to fibrosis and arrhythmias. Connexin 43 (Cx43) is the most abundant gap junctional protein in the myocardium. Current knowledge is limited regarding Cx43 remodelling in diverse cell types in the diseased myocardium and the underlying mechanism. We studied cell type-dependent changes in Cx43 remodelling due to β-AR overactivation and molecular mechanisms involved. Mouse models of isoproterenol stimulation or transgenic cardiomyocyte overexpression of β2 -AR were used, which exhibited cardiac fibrosis and up-regulated total Cx43 abundance. In both models, whereas Cx43 expression in cardiomyocytes was reduced and more laterally distributed, fibroblasts exhibited elevated Cx43 expression and enhanced gap junction communication. Mechanistically, activation of β2 -AR in fibroblasts in vitro elevated Cx43 expression, which was abolished by the β2 -antagonist ICI-118551 or protein kinase A inhibitor H-89, but simulated by the adenylyl cyclase activator forskolin. Our in vitro and in vivo data showed that β-AR activation-induced production of IL-18 sequentially stimulated Cx43 expression in fibroblasts in a paracrine fashion. In summary, our findings demonstrate a pivotal role of β-AR in mediating distinct and cell type-dependent changes in the expression and distribution of Cx43, leading to pathological gap junction remodelling in the myocardium.


Synthesis and photochemical protein crosslinking studies of hydrophilic naphthalimides.
A mixture of 4-alkylamino-1,8-naphthalimides has previously been reported to exhibit potential utility as a photochemical tissue-bonding reagent. In order to determine which constituents of the mixture were responsible for the observed tissue bonding and to facilitate study of the mechanism, we have synthesized each of the primary constituents of the mixture. Each naphthalimide synthesized has been demonstrated to photochemically crosslink proteins.


Topographic Wetness Index calculation guidelines based on measured soil moisture and plant species composition.
Soil moisture controls environmental processes and species distributions, but it is difficult to measure and interpolate across space. Topographic Wetness Index (TWI) derived from digital elevation model is therefore often used as a proxy for soil moisture. However, different algorithms can be used to calculate TWI and this potentially affects TWI relationship with soil moisture and species assemblages. To disentangle insufficiently-known effects of different algorithms on TWI relation with soil moisture and plant species composition, we measured the root-zone soil moisture throughout a growing season and recorded vascular plants and bryophytes in 45 temperate forest plots. For each plot, we calculated 26 TWI variants from a LiDAR-based digital terrain model and related these TWI variants to the measured soil moisture and moisture-controlled species assemblages of vascular plants and bryophytes. A flow accumulation algorithm determined the ability of the TWI to predict soil moisture, while the flow width and slope algorithms had only a small effects. The TWI calculated with the most often used single-flow D8 algorithm explained less than half of the variation in soil moisture and species composition explained by the TWI calculated with the multiple-flow FD8 algorithm. Flow dispersion used in the FD8 algorithm strongly affected the TWI performance, and a flow dispersion close to 1.0 resulted in the TWI best related to the soil moisture and species assemblages. Using downslope gradient instead of the local slope gradient can strongly decrease TWI performance. Our results clearly showed that the method used to calculate TWI affects study conclusion. However, TWI calculation is often not specified and thus impossible to reproduce and compare among studies. We therefore provide guidelines for TWI calculation and recommend the FD8 flow algorithm with a flow dispersion close to 1.0, flow width equal to the raster cell size and local slope gradient for TWI calculation.


[Anion-sensitive adenosine triphosphatase from membranes of rat red blood cells].
Anion-sensitive ATPase was solubilized from membranes to rat red blood cells. The effect of bicarhonate, sulfite and perchlorate on the activity of ATPase was studied. Close resemblance of the properties of ATPase of rat red blood cells and of mitochondrial ATPase was observed.


Correction to: Gadobutrol: A Review in Contrast-Enhanced MRI and MRA.
The article Gadobutrol: A Review in Contrast-Enhanced MRI and M.


Hypericum LI 160 inhibits uptake of serotonin and norepinephrine in astrocytes.
Extracts of Hypericum perforatum, commonly known as St. John's wort, are frequently used in Germany and other European countries to treat mild to moderately severe depression, but the mechanism of antidepressant activity of Hypericum is not understood. Because known mechanisms of antidepressant activity include inhibition of serotonin and/or norepinephrine uptake, we investigated the effects of standardized extracts of Hypericum LI 160 on the transport of these monoamine neurotransmitters into astrocytes, cells which surround synaptic terminals and regulate neurotransmission by means of their uptake systems. We found that LI 160 inhibited both serotonin and norepinephrine uptake in a dose-dependent manner. The two monoamine transport systems were affected differently by LI 160: for serotonin, the main effect was a 50% decrease in the rate of maximal transport, whereas for norepinephrine, the main effect was a 4.5 fold reduction in the apparent affinity of norepinephrine for its uptake sites. Upon removal of LI 160, uptake was restored, thereby indicating that the inhibition was not due to a toxic effect of Hypericum on the cells. These findings suggest that the ability of LI 160 to inhibit serotonin and norepinephrine uptake may underlie the antidepressant activity of this Hypericum extract.


Too good to go? Consumers' replacement behaviour and potential strategies for stimulating product retention.
Many products are disposed of before they have reached the end of their functional life. New technological developments and trends in fashion seem to accelerate consumers' replacement of products. From an environmental perspective, such early replacement is undesirable. In this paper, we emphasize that product replacement is not only based on rational decision making. Emotional, functional, social, epistemic and conditional values can influence the value trade-offs that consumers make during the decision to either retain an owned product or replace it with a new one. Several strategies are discussed that can increase the owned product's values and stimulate retention via product attachment, sustaining aesthetic value, stimulating product care and maintenance, and enabling upgradeability.


Intraoral repair of cosmetic restorations.
The longevity of porcelain and composite resin restorations can often be prolonged by using sound principles, up-to-date materials, and judicious attention to repair when fracture problems arise. Careful case selection and correct usage of surface treatment agents, followed by the use of a quality bonding system and restorative materials, can result in a repair that exhibits excellent retention and natural color blending. This article outlines procedures and materials to repair both resin composite and porcelain intraorally.


A novel electrochemical sensor based on phosphate-stabilized poly-caffeic acid film in combination with graphene nanosheets for sensitive determination of nitro-aromatic energetic materials.
This work offers a novel approach and sensor electrode for electrocatalytic reduction of nitro-aromatic explosives (NAEs). This sensor was created by combining electrochemically reduced graphene nanosheets (GNSs) -through cyclic voltammetric reduction of a graphene oxide colloidal solution- with phosphate-stabilized poly-caffeic acid (pCAF) film-modified glassy carbon electrode (GCE). The poly-caffeic acid-modified nonconductive electrode was stabilized with a H2PO4-/HPO42- phosphate buffer at pH 7 and made conductive. The novel electrode, called phosphate stabilized-GC/GNSs/pCAF, was characterized by electrochemical methods and scanning electron microscopy (SEM). The sensor exhibited high performance for trinitrotoluene (TNT) detection with a linear response between 50 and 500 μg L- 1 and a detection limit of 6 μg L-1. In addition to TNT, precise determinations of NAEs such as 2,4-dinitrotoluene (2,4-DNT), tetryl (2,4,6-trinitrophenyl methyl nitramine), trinitro phenol (TNP or picric acid; PA), 2,4-dinitrophenol (2,4-DNP), and 4-amino dinitrotoluene (4A-DNT, an aerobic bacterial degradation product of TNT) were made using the developed sensor electrode and DPV technique. Simultaneous quantification of TNT and DNT was performed with the aid of a computational technique known as multiple linear regression (MLR). The optimized electrode was resistant to interference effects. Satisfactory results on real samples were obtained by applying the modified electrode to the determination of TNT, tetryl, and TNP in contaminated soil. The validation of the proposed method was made against a literature LC-MS/MS method. A statistical comparison of the obtained results was provided using F- and Student's t-tests.


Proteomic characterization of pediatric craniopharyngioma intracystic fluid by LC-MS top-down/bottom-up integrated approaches.
The combination of top-down and bottom-up platforms was utilized for the LC-MS proteomic characterization of the intracystic fluid of adamantinomatous craniopharyngioma pediatric brain tumor disease. Proteins and peptides characterization was achieved by high-resolution LC-ESI-LTQ-Orbitrap-MS analysis while low-resolution LC-ESI-IT-MS was applied for the complete screening of the samples and the evaluation of the protein distribution within patients. Top-down analyses were applied to liquid/liquid extracted samples while bottom-up analyses were performed after trypsin digestion of both untreated and pretreated samples. The two proteomic approaches were complementary for the characterization of the proteome of craniopharyngioma intracystic fluid. Proteins and peptides involved in inflammation, mineralization processes and lipid transport were identified, in agreement with the calcium flecks, cholesterol granules and bone residues characteristic of this fluid. Apolipoprotein A-I, A-II, C-I and J, hemoglobin fragments, ubiquitin, α-2-HS-glycoprotein or fetuin A, α-1-antichymotrypsin, vitamin D binding protein, and α-1-acid glycoprotein were characterized. These data could be relevant for the comprehension of the processes involved in the pathogenesis of the disease and the development of the cyst and could contribute to the individuation of therapeutic targets for the reduction of the cyst volume delaying and/or avoiding invasive surgical treatments.


Dynamic Spine Hyperflexion Is Related to Vertebral Compression Fractures in Postmenopausal Women.
Previous studies on osteoporotic vertebral fractures are usually based on the neutral posture of spine; however, the fractures are usually associated with the flexion posture of spine. Therefore, we aimed to ascertain the relationship between vertebral compression fractures and thoracolumbar hyperflexion Cobb angles (TLHCobb) and determine the clinical cut-off of the TLHCobb angle. In this retrospective case-control study, TLHCobbs were collected from 154 postmenopausal women (67.45 ± 6.68 years) with vertebral compression fractures (study group) and 310 postmenopausal women (66.57 ± 8.22 years) without vertebral compression fractures (control group) from June 2017 to July 2019. Demographic data, clinical data, and quantitative computed tomography (QCT) findings were compared between the groups. Chi-squared tests, unpaired t-tests, and Mann Whitney U were used to assess the group characteristics and proportions. Logistic regression was used to examine the association between vertebral compression fractures and TLHCobb. The cut-off of the TLHCobb was determined by ROC curve and Youden's index. Fracture prevalence was higher in the higher TLHCobb study group than that in the control group [OR = 2.81 (2.15-3.67)] after adjusting for age, BMI, and QCT findings. TLHCobbs at and >20.05° were associated with an increased fracture prevalence and ORs of 2.79 (1.82-4.27) and 4.83 (3.24-7.20), respectively. TLHCobb, disk height (semiquantitative grading score) and QCT values differed between the study and control groups (p < 0.001 for all three). There were no significant differences in body mass index (BMI), or coronal TLCobb between the two groups. There was an association between the prevalence of vertebral compression fractures and TLHCobbs in postmenopausal women, and a TLHCobb > 20.05° can be an indicator of vertebral fracture.


Peptidergic innervation of the locus coeruleus cells in the human brain.
The immunocytochemical localization of corticotropin-releasing factor (CRF), thyrotropin-releasing hormone (TRH), substance P (SP), neuropeptide Y (NPY), and neurotensin (NT) were studied in the human locus coeruleus (LC) using the avidin-biotin complex (ABC) technique. The brains were obtained from 3 adult male human subjects of 36-61 years old. All of these peptides studied were present in nerve fibers and varicosities throughout the entire nucleus, where they distributed unevenly. The highest density of immunoreactive neuronal networks was generally observed in the middle and to a lesser extent in the caudal part of the nucleus, while only scattered fibers were seen in the rostral part of the LC. Among the investigated neuronal peptides, the CRF-immunopositive network was the most dense, less dense immunostaining with TRH and NPY antisera while only few SP- and NT-immunoreactive fibers were present in the nucleus. Cell bodies immunostained for the above peptides were not seen in the LC. Per analogiam with rats, fibers immunostained in the LC may be of both intrinsic and extrinsic origins.


Stability and mechanical evaluation of bovine pericardium cross-linked with polyurethane prepolymer in aqueous medium.
The present study investigates the potential use of non-catalyzed water-soluble blocked polyurethane prepolymer (PUP) as a bifunctional cross-linker for collagenous scaffolds. The effect of concentration (5, 10, 15 and 20%), time (4, 6, 12 and 24 h), medium volume (50, 100, 200 and 300%) and pH (7.4, 8.2, 9 and 10) over stability, microstructure and tensile mechanical behavior of acellular pericardial matrix was studied. The cross-linking index increased up to 81% while the denaturation temperature increased up to 12 °C after PUP crosslinking. PUP-treated scaffold resisted the collagenase degradation (0.167±0.14 mmol/g of liberated amine groups vs. 598±60 mmol/g for non-cross-linked matrix). The collagen fiber network was coated with PUP while viscoelastic properties were altered after cross-linking. The treatment of the pericardial scaffold with PUP allows (i) different densities of cross-linking depending of the process parameters and (ii) tensile properties similar to glutaraldehyde method.