PAHs in aquatic sediment in Hangzhou, China: analytical methods, pollution pattern, risk assessment and sources.
Eleven surface sediment samples, from Hangzhou section of Qiantang River and Jinghang Canal, west Lake the inland river were collected to investigate 17 polycyclic aromatic hydrocarbons (PAHs) pollution in aquatic sediments of Hangzhou. Accelerated solvent extraction(ASE) was used to extract PAHs from sediments with satisfactory recoveries. It was found that the total PAHs in the sediments ranged from 308.4 to 3037 ng/g dw, and PAHs pollution in sediments from Jinghang Canal were the heaviest. Lowest effect level (LEL) and severe effect level (SEL) sediment quality guidelines were introduced to perform risk assessment for PAHs pollution in aquatic sediments. Only one sample in Jinghang Canal had adverse impact on benthic organism. 2-3 ring PAHs had a noticeable contribution to total PAHs, especially NA, PHEN. A quantity method was used to determine the major source, the results showed petroleum origin was the chief source to PAHs pollution in all sediments with the exception of sediments from Jinghang Canal where combustion sources had a larger contribution.


In silico determination of potential antisense targets for human beta-globin variants.
The functional characterization of available genomic sequences is the major task of the research in the post-genome era. This complex task requires an integrative approach of high-throughput systems with in vitro and in vivo models in order to have a reliable evaluation of the biological function. The oligonucleotide antisense technology is one of the most promising approaches for the investigation of gene function; the crucial point of antisense experiments is the identification of optimal target sites for hybridisation. In this paper we have applied a bioinformatic tool for the recognition of optimal antisense targets. In order to evaluate the effect of mutational events on target selection we have tested the program on a sample of human beta-hemoglobin variants. The proposed algorithm software will be integrated in a web based tool at the site: http://www.nettab.org/agewa.


Infectious mononucleosis with pulmonary consolidation.
Infectious mononucleosis occurs most commonly among adolescents and young adults. Moreover, intrathoracic involvement by infectious mononucleosis, especially pulmonary consolidation, is uncommon. Thoracic computed tomography (CT) showed a massive pulmonary consolidation in the right lower lobe, multiple mediastinal lymphadenopathy, and pleural effusion in a 41-year-old man with infectious mononucleosis. Histopathology confirmed that lymphocytes and plasma cells had infiltrated the peribronchial areas and alveolar septa, and showed alveolar exudates composed of amorphous fibrinous debris, lymphocytes, and macrophages.


Carbohydrate Taste Sensitivity Is Associated with Starch Intake and Waist Circumference in Adults.
Background: Recent studies have proposed that humans may perceive complex carbohydrates and that sensitivity to simple carbohydrates is independent of sensitivity to complex carbohydrates. Variation in oral complex carbohydrate sensitivity may influence food consumption.Objective: This study aimed to investigate the associations between oral complex carbohydrate sensitivity, anthropometry, and dietary intake in adults.Methods: We assessed oral sensitivity to complex carbohydrates (maltodextrin and oligofructose) by measuring detection thresholds (DTs) and suprathreshold intensity perceptions (STs) for 34 participants, including 16 men (mean ± SEM age : 26.2 ± 0.4 y; range: 24-30 y) and 18 women (age: 29.4 ± 2.1 y; range: 24-55 y). We also measured height, weight, and waist circumference (WC) and participants completed a 4-d food diary and a food-frequency questionnaire.Results: Measurements of oral sensitivity to complex carbohydrates were significantly correlated with WC and dietary energy and starch intakes (DT: r = -0.38, P < 0.05; ST: r = 0.36-0.48, P < 0.05). When participants were grouped into tertiles, there were significant differences in WC and total energy or starch intakes for those who were more sensitive or experienced high intensity compared with those who were less sensitive or experienced low intensity. Being more sensitive or experiencing high intensity was associated with greater energy (7968-8954 kJ/d) and starch (29.1-29.8% of energy) intakes and a greater WC (88.2-91.4 cm) than was being less sensitive or experiencing low intensity (6693-7747 kJ/d, 20.9-22.2% of energy, and 75.5-80.5 cm, respectively).Conclusion: Complex carbohydrate sensing is associated with WC and consumption of complex carbohydrates and energy in adults. This trial was registered at anzctr.org.au as ACTRN12616001356459.


The influence of anisotropic membrane inclusions on curvature elastic properties of lipid membranes.
A membrane inclusion can be defined as a complex of protein or peptide and the surrounding significantly distorted lipids. We suggest a theoretical model that allows for the estimation of the influence of membrane inclusions on the curvature elastic properties of lipid membranes. Our treatment includes anisotropic inclusions whose energetics depends on their in-plane orientation within the membrane. On the basis of continuum elasticity theory, we calculate the inclusion-membrane interaction energy that reflects the protein or peptide-induced short-ranged elastic deformation of a bent lipid layer. A numerical estimate of the corresponding interaction constants indicates the ability of inclusions to sense membrane bending and to accumulate at regions of favorable curvature, matching the effective shape of the inclusions. Strongly anisotropic inclusions interact favorably with lipid layers that adopt saddlelike curvature; such structures may be stabilized energetically. We explore this possibility for the case of vesicle budding where we consider a shape sequence of closed, axisymmetric vesicles that form a (saddle-curvature adopting) membrane neck. It appears that not only isotropic but also strongly anisotropic inclusions can significantly contribute to the budding energetics, a finding that we discuss in terms of recent experiments.


Family history and risk of breast cancer in New Zealand.
A national population-based case-control study was used to assess the influence on breast cancer risk of a family history of the disease and the possibility of an interaction with reproductive risk factors. A total of 891 women aged 25-54 years with a first diagnosis of breast cancer and 1,864 control subjects randomly selected from the electoral rolls were interviewed. Age-adjusted relative risks (RR) of breast cancer were similar for mothers (RR = 2.3) and sisters (RR = 2.7) but somewhat higher for first-degree (RR = 2.6) than for second-degree (RR = 1.7) relatives. Cases reporting a first- or second-degree relative with breast cancer were no more likely to be diagnosed at an early age than those with no family history. With regard to the age at diagnosis of the relative, the RR was higher if breast cancer had been diagnosed before the age of 45 years than later; this was true for first-degree as well as for second-degree relatives. In women with no family history, the falling RRs with increasing age at menarche reflected the usual pattern, but no such trend was apparent in those reporting a mother or sister with breast cancer. For age at first full-term pregnancy, parity, breast-feeding, menopausal status, infertility, history of benign breast disease and body mass index, no evidence was seen of effect modification by a family history of breast cancer. Mothers of cases had about twice the cumulative rate of breast cancer as mothers of controls, a similar difference being seen between sisters of cases and sisters of controls.


Genotypes and phenotypes heterogeneity in PIK3CA-related overgrowth spectrum and overlapping conditions: 150 novel patients and systematic review of 1007 patients with PIK3CA pathogenetic variants.
Postzygotic activating PIK3CA variants cause several phenotypes within the PIK3CA-related overgrowth spectrum (PROS). Variant strength, mosaicism level, specific tissue involvement and overlapping disorders are responsible for disease heterogeneity. We explored these factors in 150 novel patients and in an expanded cohort of 1007 PIK3CA-mutated patients, analysing our new data with previous literature to give a comprehensive picture. We performed ultradeep targeted next-generation sequencing (NGS) on DNA from skin biopsy, buccal swab or blood using a panel including phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway genes and GNAQ, GNA11, RASA1 and TEK. Additionally, 914 patients previously reported were systematically reviewed. 93 of our 150 patients had PIK3CA pathogenetic variants. The merged PROS cohort showed that PIK3CA variants span thorough all gene domains, some were exclusively associated with specific PROS phenotypes: weakly activating variants were associated with central nervous system (CNS) involvement, and strongly activating variants with extra-CNS phenotypes. Among the 57 with a wild-type PIK3CA allele, 11 patients with overgrowth and vascular malformations overlapping PROS had variants in GNAQ, GNA11, RASA1 or TEK. We confirm that (1) molecular diagnostic yield increases when multiple tissues are tested and by enriching NGS panels with genes of overlapping 'vascular' phenotypes; (2) strongly activating PIK3CA variants are found in affected tissue, rarely in blood: conversely, weakly activating mutations more common in blood; (3) weakly activating variants correlate with CNS involvement, strong variants are more common in cases without; (4) patients with vascular malformations overlapping those of PROS can harbour variants in genes other than PIK3CA.


Biosynthesis of Cutin omega-Hydroxylation of Fatty Acids by a Microsomal Preparation from Germinating Vicia faba.
omega-Hydroxylation of fatty acids, which is a key reaction in the biosynthesis of cutin and suberin, has been demonstrated for the first time in a cell-free preparation from a higher plant. A crude microsomal fraction (105,000g pellet) from germinating embryonic shoots of Vicia faba catalyzed the conversion of palmitic acid to omega-hydroxypalmitic acid. As the crude cell-free preparation also catalyzes the formation of other hydroxy acids such as alpha- and beta-hydroxy acids, the omega-hydroxylation product was identified by gas chromatography on a polyester column and reverse phase, high performance liquid chromatography, two techniques which were shown to resolve the positional isomers. Gas chromatographic analysis of the dicarboxylic acid obtained by CrO(3) oxidation of the enzymic product also confirmed the identity of the enzymic omega-hydroxylation product. This enzymic hydroxylation required O(2) and NADPH, but substitution of NADH resulted in nearly half the reaction rate obtained with NADPH. Maximal rates of omega-hydroxylation occurred at pH 8 and the rate increased in a sigmoidal manner with increasing concentrations of palmitic acid. This omega-hydroxylation was inhibited by the classical mixed function oxidase inhibitors such as metal chelators (o-phenanthroline, 8-hydroxyquinoline, and alpha,alpha-dipyridyl), NaN(3) and thiol reagents (N-ethylmaleimide and p-chloromercuribenzoate). As expected of a hydroxylase, involving cytochrome P(450), the present omega-hydroxylase was inhibited by CO and this enzyme system showed unusually high sensitivity to this inhibition; 10% CO caused inhibition and 30% CO completely inhibited the reaction. Another unusual feature was that the inhibition caused by any level of CO could not be reversed by light (420-460 nm).


Outcome of invasive treatment modalities on back pain and sciatica: an evidence-based review.
Within the framework of evidence-based medicine high-quality randomised trials and systematic reviews are considered a necessary prerequisite for progress in orthopaedics. This paper summarises the currently available evidence on surgical and other invasive procedures for low back pain. Results of systematic reviews conducted within the framework of the Cochrane Back Review Group were used. Data were gathered from the latest Cochrane Database of Systematic Reviews 2005, Issue 2. The Cochrane reviews were updated using the evidence summary on surgery and other invasive procedures from the COST B13 European Guidelines for the Management of Acute and Chronic Non-Specific Low Back Pain. Facet joint, epidural, trigger point and sclerosant injections have not clearly been shown to be effective and can consequently not be recommended. There is no scientific evidence on the effectiveness of spinal stenosis surgery. Surgical discectomy may be considered for selected patients with sciatica due to lumbar disc prolapses that fail to resolve with the conservative management. Cognitive intervention Combined with exercises is recommended for chronic low back pain, and fusion surgery may be considered only in carefully selected patients after active rehabilitation programmes during 2 years time have failed. Demanding surgical fusion techniques are not better than the traditional posterolateral fusion without internal fixation.


Smooth muscle tumours of the upper gastrointestinal tract.
Forty-six patients with smooth muscle tumours of the stomach and small intestine were treated surgically at the Princess Alexandra Hospital between 1970 and 1986. Leiomyomas were three times more common than leiomyosarcomas, but malignant tumours occurred more frequently in the small intestine than in the stomach. Gastric tumours tended to present with gastrointestinal bleeding, in contrast to intestinal lesions which presented predominantly with abdominal pain. Although leiomyomas tend to be smaller at operation than leiomyosarcomas, the size of a smooth muscle tumour is not reliable in discriminating between benign and malignant lesions. Therefore all smooth muscle tumours of the upper gastrointestinal tract should be excised as widely as possible, including local lymphatics in the dissection where practicable, so as to maximize the likelihood of radical extirpation of malignant lesions. Approximately one-third of patients with leiomyosarcomas have metastases at the time of surgery; the 5 year survival rate after surgical treatment of leiomyosarcomas of the upper gastrointestinal tract is less than 50%.


Galactose-1-Phosphate Uridyltransferase Activities in Different Genotypes: A Retrospective Analysis of 927 Samples.
Classic galactosemia is an inherited disorder of galactose metabolism caused by the impaired activity of galactose-1-phosphate uridyltransferase (GALT). Untreated galactosemia is life-threatening; however, early dietary intervention prevents mortality and reduces morbidity associated with this disease. The diagnosis of galactosemia includes the measurement of GALT activity in red blood cells (RBC) and GALT gene analysis. In this study, we evaluate GALT activity in different genotypes using the results of combined biochemical and molecular testing in 927 samples. GALT activity in RBC was measured by LC-MS/MS. The analysis of the GALT gene was performed by targeted gene analysis and/or full gene sequencing. Samples were assigned based on the presence of pathogenic (G) or Duarte 2 (D) variants, or their absence (Neg), to G/G, D/G, G/Neg, D/D, D/Neg, and Neg/Neg genotypes. Finite mixture models were applied to investigate distributions of GALT activities in these genotypes. The reference ranges were determined using the central 95% of values of GALT activities. The ranges of GALT activity in G/G, D/G, G/Neg, D/D, D/Neg, and Neg/Neg genotypes are 0.0 to 0.7 μmol·h-1 gHb-1, 3.1 to 7.8 μmol·h-1 gHb-1, 6.5 to 16.2 μmol·h-1 gHb-1, 6.4 to 16.5 μmol·h-1 gHb-1, 12.0 to 24.0 μmol·h-1 gHb-1, and 19.4 to 33.4 μmol·h-1 gHb-1, respectively. The GALT activity ranges established in this study are in agreement with the expected impact of the genotype on the enzymatic activity. Molecular findings should be interpreted in view of biochemical results to confirm genotype-phenotype correlation.


Effects of motoric requirements on the acquisition of manual sign responses by severely handicapped students.
Eight severely handicapped school-aged students were given training on communicative signs that varied according to iconic or abstract, touch or nontouch, and symmetrical or asymmetrical sign dimensions to determine the effects of motoric requirements on sign acquisition. A 2 X 2 Latin square design repeated between and within students was used. Symmetrical signs were acquired significantly faster than were asymmetrical signs, and touch signs were acquired significantly faster than were nontouch signs. Results of the acquisition of iconic vs. abstract signs were inconclusive.


Increased beat-to-beat variation in diastolic phase percentages in patients with congestive heart failure.
Diastolic time (DT) may reflect the functioning status of cardiac relaxation/diastolic filling. Previous studies shown that beat-to-beat variation in RR interval (i.e., HRV) is preferentially expressed in the variation in DT series, raising up a question that whether DT possesses intrinsic variation, or whether the DT variation is simply a surrogate of HRV without additional information. In this study, we defined the diastolic phase percentages (DP) by correcting DT by the corresponding RR interval and proposed to analyze DP variation (DPV) in order to eliminate the masking effect of HRV. We studied DPV of 60 patients with congestive heart failure (CHF) and 60 healthy control subjects. Radial artery pressure (RAP) was monitored in synchrony with electrocardiography (ECG) for 5 min in order to extract the proposed DPV. Additionally, DPV was corrected by the individual mean DP level which resulted in the coefficient of DPV (cDPV). The differences in DPV and cDPV between the two groups were determined by linear regression models controlled for age and sex. Results showed that both DPV and cDPV increased significantly in CHF patients compared with healthy control subjects (both p <; 0.05). Those results, highly endorsing the existence of intrinsic physiological variation in DT, may suggest that CHF patients have less stable cardiac relaxation (that is not due to HRV) or/and less stable contractility (since the diastolic and systolic phases are mutually complementary). This study may provide helpful reference for the noninvasive evaluation of cardiac functionality and for the further understanding of multiple physiological variabilities.


Mechanisms of the charge transfer in IrQ(ppy)2-5Cl dual-emitter compound.
The synthesis of IrQ(ppy)2-5Cl has the advantage of a dual phosphorescence (green and red) which comes from the two ligands, phenylpyridine and quinoline. Their spectroscopic properties evidences the absorption range between 350 nm to 700 nm which is composed from the singlet and triplet states, as a result of hybridizations between Ir and the two ligands, the first one being at 625 nm. The first low energy state comes from the quinoline ligand and is responsible for the red phosphorescence at 660 nm, as results from the Density Functional Theory (DFT) analysis. The hybridization between Ir 5d orbitals and pi ligand orbitals shows strong metallic character with phenylpyridine orbitals (66% and 43%) and weak metallic character with quinoline ligand (16.8%). This fact suggests weak phosphorescence intensity in the emission spectra. Population analysis of each metallic orbital shows a small charge delocalization on the quinoline ligand for the first molecular orbital and a strong delocalization on the phenylpyridine ligands. Solvation effects induce a tuning process for the phosphorescence by changing of the matrix of the organometallic compounds which can be adjusted by the strength of intermolecular dipole-dipole interactions, using a doped guest-host molecular organic thin film system.


ATM Protein Kinase: Old and New Implications in Neuronal Pathways and Brain Circuitry.
Despite that the human autosomal recessive disease ataxia telangiectasia (A-T) is a rare pathology, interest in the function of ataxia-telangiectasia mutated protein (ATM) is extensive. From a clinical point of view, the role of ATM in the central nervous system (CNS) is the most impacting, as motor disability is the predominant symptom affecting A-T patients. Coherently, spino-cerebellar neurodegeneration is the principal hallmark of A-T and other CNS regions such as dentate and olivary nuclei and brain stem are implicated in A-T pathophysiology. Recently, several preclinical studies also highlighted the involvement of ATM in the cerebral cortex and hippocampus, thus extending A-T symptomatology to new brain areas and pathways. Here, we review old and recent evidence that largely demonstrates not only the historical ATM account in DNA damage response and cell cycle regulation, but the multiple pathways through which ATM controls oxidative stress homeostasis, insulin signalling pathways, epigenetic regulation, synaptic transmission, and excitatory-inhibitory balance. We also summarise recent evidence on ATM implication in neurological and cognitive diseases beyond A-T, bringing out ATM as new pathological substrate and potential therapeutic target.


Effects of sodium bicarbonate on VO2 kinetics during heavy exercise.
Sodium bicarbonate was used to investigate the effect of blood pH on VO2 kinetics during heavy exercise. On separate days, 10 active subjects performed two 6-min cycling bouts (208 +/- 12 W) at 25 W above their ventilatory threshold. Each subject ingested 0.3 g x kg(-1) of sodium bicarbonate with approximately 1 L of water or water alone 1 h before exercise. VO2 kinetics were examined by means of a three-component mono-exponential model. Bicarbonate ingestion caused a significant increase in the preexercise blood pH (7.512 +/- 0.009 vs 7.425 +/- 0.007; P < 0.001). In the bicarbonate trial, the time constant for the rapid component (27.9 +/- 3.5 s) was slower than the control trial (20.8 +/- 2.4 s; P = 0.017). The higher blood pH after bicarbonate ingestion would have diminished local blood flow and caused a leftward shift of the oxygen-hemoglobin dissociation curve both of which would slow oxygen delivery to working muscle. In addition, bicarbonate ingestion diminished the amplitude of the slow component 29% (463 +/- 43 vs 649 +/- 53 mL x min(-1); P = 0.040). The primary cause of the slow component during heavy exercise is fatigue of working fibers and an accompanying increase of motor unit recruitment. Elevated plasma bicarbonate concentration is reported to stimulate the efflux of H from muscle fibers and to increase intramuscular pH. The slower time constant during the rapid component suggested that oxygen delivery is a limiting factor of VO2 kinetics during the onset of heavy exercise. Also, these results imply that bicarbonate ingestion diminished fatigue in working fibers during the slow component.


Effect of endothelin-1 on responses of isolated blood vessels to vasoconstrictor agonists.
The effect of endothelin-1 (ET-1) on vasoconstrictor responses of the endothelium-denuded perfused rabbit ear artery to 5-hydroxytryptamine (5-HT), histamine, and vasopressin (VP) was studied. In low concentrations with no vasoconstrictor action (0.1 and 0.3 nM), and in a concentration that increased the perfusion pressure by 70 mm Hg (1 nM), ET-1 significantly enhanced responses to the agonists studied; this enhancement was apparently mediated by an increased influx of extracellular calcium through voltage-operated channels, as it was abolished by the calcium channel antagonist nicardipine (10 nM). In contrast, higher concentrations of ET-1 (3 and 10 nM) inhibited responses to VP and 5-HT and this inhibitory effect was accentuated in the presence of nicardipine. The possible mechanism by which ET-1 exerts this inhibitory effect on vasoconstrictor responses is discussed. Because ET-1 is released from endothelial cells that are immediately adjacent to vascular smooth muscle cells, these modulatory effects of ET-1 on responses to endogenously present vasoconstrictors may play a role in vascular function.


Gh is produced by the testis of Japanese eel and stimulates proliferation of spermatogonia.
Gh plays important roles in development, somatic growth and gametogenesis in vertebrates. To determine the physiological role of Gh in reproduction in male teleosts, the expression of genes encoding Gh and the two Gh receptors (Ghrs) during spermatogenesis, and the action of Gh in vitro was examined using the Japanese eel (Anguilla japonica). gh, ghr1 and ghr2 mRNA transcripts were detected in all spermatogenic stages. In situ hybridization showed the presence of ghr1 and ghr2 mRNA in the germ cells. Immunohistochemistry using an antiserum against eel Gh indicated that Gh protein was localized to Sertoli cells surrounding the germ cells in early spermatogenesis. Recombinant eel Gh induced spermatogonial proliferation in a testis organ culture system, an effect that was independent from the production of steroid hormones or Igf1. This study identifies a role for eel Gh in the regulation of early spermatogenesis, particularly in the mitotic phase of spermatogenesis, that is not mediated by either steroid hormones or Igf1 production.


Hon v. Stroh Brewery Company: what do we mean by "moderate" and "heavy" drinking?
Although widely used, drinking terms such as "light,"' "moderate," and "heavy" are unstandardized and, as a result, public health messages using these terms may convey confusing information. As an initial attempt in providing such standardization, the present study surveyed public definitions for these terms. "Light" drinking was operationally defined as 1.4-2.4 drinks/day; "moderate" drinking was defined as 2.5-3.6 drinks/day; and "heavy" drinking was defined as 3.7 drinks/day and above. These ranges, however, were dependent on the respondent's gender, age, socioeconomic status, and especially the respondent's self-reported tolerance. Males had a higher threshold of consumption for "moderate" and "heavy" drinking than women. Older respondents likewise assigned a higher threshold for these terms than younger respondents. As respondent income increased, the threshold for "heavy" drinking decreased. The heaviest drinkers had a higher threshold for assigning the "heavy" label than did any other group. Ethnicity did not significantly affect these ranges, and religion only affected the threshold for "heavy" drinking. Because reseachers ultimately rely on terms such as "moderate" or ":heavy" to communicate their findings to colleagues and the public, it would seem apposite for them to agree on operational definitions for such terms. It would also seem appropriate to consider the operational definitions the public uses when referring to these terms to promote credibility of research findings and appropriate changes in behavior.


Minor neurological and perceptuo-motor deficits in children with congenital muscular dystrophy: correlation with brain MRI changes.
Diffuse white matter changes on magnetic resonance imaging (MRI) have been a consistent feature in some children with the "pure" form of congenital muscular dystrophy (CMD) in which there are no structural changes in the brain or severe mental retardation. The aim of this study was to assess fine motor and perceptuo-motor abilities in children with CMD with and without MRI changes. Twenty-two children with "pure" CMD were investigated with a standard neurological examination and a battery of tests (Manual dexterity from the Movement ABC, test of visual-motor integration, Zurich Neuromotor test) which have already been used to detect minor neurological signs related to white matter changes. The cohort was then divided in two groups for analysis depending on the presence or the absence of diffuse white matter changes. A significant difference was found for all the tests between the group of the CMD children with normal MRI and the group with diffuse white matter changes. The manual dexterity and the Zurich Neuromotor tests showed a greater sensitivity than the test of visual-motor integration, which had some false negatives. It is of interest that in the group with diffuse white matter changes the presence of contractures or weakness did not seem to affect the quality of the performance; all these children scored abnormally on the test, irrespective of the severity or the extent of contractures and weakness. In contrast, in children with normal MRI severe contractures and weakness did affect the performances. Our results demonstrate that perceptuo-motor difficulties and minor neurological soft signs are a consistent feature in CMD children with diffuse MRI changes but not with normal MRI.(ABSTRACT TRUNCATED AT 250 WORDS)


[Myelodysplasias and systemic diseases. A non-fortuitous association].
Myelodysplastic syndromes are clonal hematologic disorders, expanded from myeloid stem cells. A primitive immunologic disorder is discussed. This hypothesis could explain a non-casual association with systemic diseases. The aim of our study is to test this hypothesis. We retrospectively investigated the data of 60 patients with myelodysplastic syndromes (group I) hospitalized in our unit from 1990 to 1999. The frequency of systemic disorders was screened and compared to controls (group II). Group II consisted of 120 patients matched for age and sex and hospitalized in the same hospital during the same period. Sixty patients were included (mean age: 83 years old). Myelodysplastic syndrome subtypes were refractory anemia with excessive blasts (52%), refractory anemia (43%) and sideroblastic anemia (5%). Fourteen cases of systemic manifestations were reported in group I (23%) and five in the controls (4%) (P < 0.0001). Systemic manifestations in group I included vasculitis in six cases (42%), polyarthritis in three cases (21%), systemic amyloidosis AA in two cases (14%), relapsing polychondritis in one case, pyoderma gangrenosum in one case and celiac disease associated with a systemic granulomatosis in one case. In the controls, vasculitis was present in four cases and polyarthritis in one. Median age at onset of myelodysplastic syndrome was not influenced by the association with systemic disorders which, in return, have not influenced the myelodysplastic syndromes' subtypes. Myelodysplastic syndromes succeeded to systemic manifestations in 71.4% of cases and could not be attributed to immunosuppressive therapy. The association of myelodysplastic syndromes with systemic manifestations seems not to be casual. It raises the hypothesis of a primitive immunological disorder in both diseases. Moreover, the description of two cases of systemic amyloidosis and one case of pyoderma gangrenosum might suggest an additional disorder of macrophages or granular cells.


Planning, designing, operating, and regulating a geologic sequestration repository as an underground landfill--a review.
Geologic sequestration appears to be a technically feasible method of storing carbon dioxide in underground aquifers in order to lower greenhouse gas emissions into the atmosphere. The overall feasibility of geologic sequestration is still in question and as such, has been the focus of intense research over the past decade. Researchers have looked to the oil/gas industry and water well industry for lessons learned and technical knowledge, however, a better industry to emulate may well be the waste industry. Viewing geologic sequestration repositories as underground landfills has a great many benefits. First, there is a plethora of existing research and investigations that are directly analogous to geologic sequestration projects. Second, the regulatory framework is rather mature and can be easily adapted to serve geologic sequestration. This paper conducts an extensive literature search of the environmental, waste, and geologic sequestration literature to ascertain planning, design, and operational methodologies, lessons learned, and concepts that are directly useful for geologic sequestration to improve the technical and regulatory framework. Lastly, the paper uses a hypothetical underground landfill geologic sequestration site (ULGSS) in Florida, USA to discuss some of the findings and implications from the literature. It is concluded that there are a number of literature findings from the waste and environmental arena that should be adapted for geologic sequestration.


Exceptional size-dependent activity enhancement in the electroreduction of CO2 over Au nanoparticles.
The electrocatalytic reduction of CO2 to industrial chemicals and fuels is a promising pathway to sustainable electrical energy storage and to an artificial carbon cycle, but it is currently hindered by the low energy efficiency and low activity displayed by traditional electrode materials. We report here the size-dependent catalytic activity of micelle-synthesized Au nanoparticles (NPs) in the size range of ∼1-8 nm for the electroreduction of CO2 to CO in 0.1 M KHCO3. A drastic increase in current density was observed with decreasing NP size, along with a decrease in Faradaic selectivity toward CO. Density functional theory calculations showed that these trends are related to the increase in the number of low-coordinated sites on small NPs, which favor the evolution of H2 over CO2 reduction to CO. We show here that the H2/CO product ratio can be specifically tailored for different industrial processes by tuning the size of the catalyst particles.


[Expression of epidermal growth factor receptor and the oncogene c-erbB2 on pulmonary fibrosis induced by bleomycin in rats].
To study the expression of the epidermal growth factor receptor (EGFR) and the oncogene c-erbB2 on pulmonary fibrosis induced by bleomycin (BLM) in rats. Fifty-four Wistar rats were randomly divided into three groups, the pulmonary fibrosis group (BLM), Iressa group and the control group. There were 18 rats in each group. Control group were injected with saline 0.2-0.3 ml in trachea. Iressa group and BLM group were injected with BLM intratracheal. After the fibrosis models were build, Iressa group were given orally Iressa (200 mg/kg)1 h before modeling in Iressa group, saline were fed 10 ml/kg in BLM group and control group. The three groups were fed 5 times per week; and were sacrificed after treatment on days 1, 14 and 28 respectively. The lungs were harvested for histological studies. The lung tissue in Iressa group showed fibrosis and inflammatory cell infiltration, the same as shown in the BLM group. The pulmonary fibrosis score was significantly lower than the BLM group on the 28 th day (2.17 +/- 0.41 vs 3.50 +/- 0.84, P < 0.01). Compared with the control group, c-erbB2 and EGFR were hyper expressed significantly both in BLM group and Iressa group at all time points (P < 0.01); c-erbB2 expression had no changes between the Iressa group and the BLM (P > 0.05), that were gradually decreased, and was significantly different at each time point (P < 0.01). EGFR expression was increased gradually on the 14th and 28th day (0.17 +/- 0.02 and 0.28 +/- 0.04) in Iressa group ,that was significantly lower than the BLM group (0.27 +/- 0.04 and 0.34 +/- 0.02) (P < 0.01). EGFR expression increased significantly on the 28th day than on the 14th day in the Iressa group (P < 0.01). The expression of C-erbB2 and EGFR are enhanced in different stages of alveolitis and pulmonary fibrosis, c-erbB2 and EGFR may be participated in different stages of pulmonary fibrosis.


Healing at the Interface Between Autologous Block Bone Grafts and Recipient Sites Using n-Butyl-2-Cyanoacrylate Adhesive as Fixation: Histomorphometric Study in Rabbits.
The aim of the present split-mouth (split-plot) study was to describe the sequential healing in the interface between autologous bone grafts and recipient parent bone, fixed using an n-butyl-2-cyanoacrylate adhesive with or without an additional titanium fixation screw. Bone grafts were collected from the calvaria and fixed to the lateral aspect of the mandible in 24 rabbits. The cortical layers of the recipient sites were perforated, and the grafts were randomly fixed using an n-butyl-2-cyanocrylate adhesive, either alone or in conjunction with a 1.5 mm × 6.0 mm titanium fixation screw. The animals were sacrificed after 3, 7, 20, and 40 days, and histomorphometric evaluations of the interface between graft and parent bone were performed. Only 2 of 6 grafts in each group were partially incorporated to the parent bone after 40 days of healing. The remaining grafts were separated from the parent bone by adhesive and connective tissue. It was concluded that the use of n-butyl-2-cyanoacrylate as fixation of an autologous bone graft to the lateral aspect of the mandible was able to maintain the fixation over time but did not incorporate the graft to the recipient sites. Use of fixation screws did not improve the healing.


Formation of the quasi-planar B56 boron cluster: topological path from B12 and disk aromaticity.
Formation and stability of the B56 boron cluster were investigated using a topological approach and the disk aromaticity model. An extensive global energy minimum search for the B56 system which was carried out by means of the Mexican Enhanced Genetic Algorithm (MEGA) in conjunction with density functional theory computations, confirms a quasi-planar structure as its energetically most stable isomer. Such a structural motif is derived by applying a topological leapfrog operation to a B12 form. Its high thermodynamic stability can be explained by the disk aromaticity model in which the delocalization of its π orbitals can be assigned to the levels of a particle in a circular box with the [(1σ)2 (1π)4 (1δ)4 (1φ)4 (2σ)2 (1γ)4 (2π)4 (2δ)4 (1η)4 (2φ)4 (1θ)2] electronic configuration. This π delocalization is confirmed by other delocalization indices. While the B56 has a similar electron delocalization to that of the quasi-planar B50, they have opposite magnetic ring current properties because of the symmetry selection rules of their HOMO-LUMO electronic transitions. The π delocalization in the boron clusters is larger at long distances as compared to carbon clusters at similar sizes, but such a trend is reversed at shorter distances.


Cardiomyocyte damage control in heart failure and the role of the sarcolemma.
The cardiomyocyte plasma membrane, termed the sarcolemma, is fundamental for regulating a myriad of cellular processes. For example, the structural integrity of the cardiomyocyte sarcolemma is essential for mediating cardiac contraction by forming microdomains such as the t-tubular network, caveolae and the intercalated disc. Significantly, remodelling of these sarcolemma microdomains is a key feature in the development and progression of heart failure (HF). However, despite extensive characterisation of the associated molecular and ultrastructural events there is a lack of clarity surrounding the mechanisms driving adverse morphological rearrangements. The sarcolemma also provides protection, and is the cell's first line of defence, against external stresses such as oxygen and nutrient deprivation, inflammation and oxidative stress with a loss of sarcolemma viability shown to be a key step in cell death via necrosis. Significantly, cumulative cell death is also a feature of HF, and is linked to disease progression and loss of cardiac function. Herein, we will review the link between structural and molecular remodelling of the sarcolemma associated with the progression of HF, specifically considering the evidence for: (i) Whether intrinsic, evolutionary conserved, plasma membrane injury-repair mechanisms are in operation in the heart, and (ii) if deficits in key 'wound-healing' proteins (annexins, dysferlin, EHD2 and MG53) may play a yet to be fully appreciated role in triggering sarcolemma microdomain remodelling and/or necrosis. Cardiomyocytes are terminally differentiated with very limited regenerative capability and therefore preserving cell viability and cardiac function is crucially important. This review presents a novel perspective on sarcolemma remodelling by considering whether targeting proteins that regulate sarcolemma injury-repair may hold promise for developing new strategies to attenuate HF progression.


Pathophysiology of traumatic brain injury.
Traumatic brain injury (TBI) is considered an epidemic that continues to compromise the welfare of humankind. Despite the extensive efforts invested in countering this clinical health problem, current clinical science and technology still fall short of providing a pharmacological cure for TBI rendering tens of thousands of TBI patients vulnerable to its detrimental sequelae. Over the past 30 years, the understanding of the pathophysiological mechanisms of TBI indicates that the pathology of TBI is biphasic. It comprises 2 injuries; the primary and the secondary injuries. The primary injury occurs simultaneously with the impact that caused the injury, which explains why this injury is not amenable to acute intervention. Whereas the secondary injury is a composite of interwoven pathophysiological responses that commence after the initial trauma leading to delayed, non-mechanical impairment of neuronal structure and function. In this review, we aim to highlight the main pathophysiological mechanisms that take place in the primary and secondary phases of traumatic brain injury.


Bifunctional Oxygen Electrocatalysis of N, S-Codoped Porous Carbon with Interspersed Hollow CoO Nanoparticles for Rechargeable Zn-Air Batteries.
Exploring efficient bifunctional oxygen electrocatalysts is beneficial to promote the practical applications for rechargeable Zn-air batteries. Herein, a high-efficiency one-pot method is developed to synthesize porous carbon with N, S doping and embedded hollow cobalt oxide nanoparticles. The coordination of polyethyleneimine molecules with cobalt ions enables the formation of organic-inorganic precursors via the co-precipitation with lignosulfonate because of the electrostatic interaction. Under thermal treatment, the hollow cobalt oxide nanoparticles can be well dispersed among the carbon matrix codoped with N, S. The as-prepared composite catalysts exhibit efficient bifunctional activity for electrochemical reduction and evolution reactions of oxygen, thanks to the N, S codoping nature and the hollow cobalt oxide with abundant oxygen vacancies. The bifunctional catalytic activity renders the assembly of high-performance Zn-air battery in an aqueous electrolyte with a specific capacity of 745 mA h gZn-1 and good cycling stability for over 100 h. More importantly, the all-solid-state Zn-air battery is assembled with a polymer-based electrolyte, also exhibiting good cycling stability and flexibility under various bending status.


Evaluation of dairy food processing wash water solids as a protein source: II. Microbial protein synthesis, duodenal nitrogen flow, and small intestinal amino acid disappearance.
Twelve ruminally, duodenally, and ileally-cannulated Hereford heifers (average initial BW 313 +/- 20 kg) were used in a replicated experiment to evaluate dairy food processing wash water solids (WWS) as a protein source. Heifers were fed 2.8 kg of chopped (7.6 cm) hay and one of three supplements (1.5 kg/d, DM basis). Supplements were formulated to be similar in energy and contained 1.0 (control), 23.2 (WWS), and 21.6% (soybean meal; SBM) CP on an OM basis. Total N and nonammonia N entering the duodenum (g/d) were greater (P less than .10) for heifers fed WWS and SBM supplements than for controls. Bacterial N flow (g/d) at the duodenum was less (P less than .10) for controls (43.9) than for WWS- (63.9) and SBM- (69.9) supplemented heifers. Feed escape N (g/d) was greater (P less than .10) for WWS-fed heifers than for those fed SBM (32.1 vs 20.7 g/d, respectively). Total tract N digestion (g/d) was greatest (P less than .10) for SBM, intermediate for WWS, and least for control heifers. Microbial protein synthesis (g/kg of OM intake) was enhanced (P less than .10) by WWS and SBM supplementation, but efficiency of synthesis (g/kg of OM fermented) did not differ among treatments. Essential amino acid (AA) disappearance in the small intestine (g/d) was less (P less than .10) for control than for the other two treatments. Nonessential AA disappearance was greatest (P less than .10) for the WWS and least (P less than .10) for the control treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Registered report: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis.
The Reproducibility Project: Cancer Biology seeks to address growing concerns about reproducibility in scientific research by conducting replicating selected results from a number of high-profile papers in the field of cancer biology. The papers, which were published between 2010 and 2012 were selected on the basis of citations and Altimetric scores (Errington et al., 2014). This Registered report describes the proposed replication plan of key experiments from 'Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis' by Goetz and colleagues, published in Cell in 2011 (Goetz et al., 2011). The key experiments being replicated are those reported in Figures 7C (a-d), Supplemental Figure S2A, and Supplemental Figure S7C (a-c) (Goetz et al., 2011). In these experiments, which are a subset of all the experiments reported in the original publication, Goetz and colleagues show in a subcutaneous xenograft model that stromal caveolin-1 remodels the intratumoral microenvironment, which is correlated with increased metastasis formation. The Reproducibility Project: Cancer Biology is a collaboration between the Center for Open Science and Science Exchange and the results of the replications will be published in eLife.


Injuries in Swedish elite basketball.
All Swedish male and female elite basketball players were interviewed concerning their injuries during 1981/1982. Fifty-eight percent of the male and 62% of the female players reported injuries. The injury frequency was 2.5 injuries/1,000 activity-hours in male and 2.85 injuries/1,000 hours of activity in female players. This corresponds to 8.6 injuries/male team/season and 7.5 injuries/female team/season. An ankle twist was the most common injury (52%) while a knee injury was involved in 18%. Prophylactic orthoses for knee and ankle are suggested.


The effect of topical arnica on muscle pain.
The herb Arnica montana, in topical formulations, has been reputed to decrease bruising and muscle pain. This claim has been inadequately and incompletely addressed. To determine whether topical A. montana cream could decrease subjective leg pain following calf raises. Secondary outcomes were effects on ankle range of motion and muscle tenderness. A randomized, double-blind, placebo-controlled trial was conducted in 53 subjects. Active range of motion was measured in both ankles, and then a series of calf-raises were completed according to a standardized protocol. Each participant received 2 tubes of cream, 1 with active arnica and 1 with placebo. The creams were applied to the lower legs immediately after the exercise, and again at 24 and 48 hours postexercise according to the "RIGHT" or "LEFT" labels. At 48 hours postexercise, subjects had their ankle range of motion and muscle tenderness measured. Subjects used the analog scale to rate pain in each leg at baseline, 24 hours, 48 hours, and 72 hours. No significant differences in pain scores were seen before exercise (arnica: 0.07 vs placebo: 0.09, p = 0.32). Pain scores on legs treated with arnica were higher than scores on those receiving placebo 24 hours after exercise (3.04 vs 2.36, respectively; p < 0.005). Pain scores on day 3 (arnica: 3.44 vs placebo: 3.20, p = 0.66) and day 4 (arnica: 2.36 vs placebo: 2.31, p = 0.62) were not significantly different. There was no difference in muscle tenderness (arnica: 1.05 vs placebo: 1.05, p = 1.0). Ankle range of motion did not differ significantly on either day 1 (arnica: 64.70 degrees vs placebo: 66.15, p = 0.352 or day 3 (arnica: 63.32 degrees vs placebo: 65.94, p = 0.058). Rather than decreasing leg pain, arnica was found to increase leg pain 24 hours after eccentric calf exercises. This effect did not extend to the 48-hour measurement.


Analysis of the Taxonomy and Pathogenic Factors of Pectobacterium aroidearum L6 Using Whole-Genome Sequencing and Comparative Genomics.
Soft rot pectobacteria are devastating plant pathogens with a global distribution and a broad host range. Pectobacterium aroidearum L6, previously isolated from leaves of Syngonium podophyllum, is a pectolytic bacterial pathogen that causes typical soft rot on S. podophyllum. There is a shortage for genome data of P. aroidearum, which seriously hinders research on classification and pathogenesis of Pectobacterium. We present here the complete genome sequence of P. aroidearum L6. The L6 strain carries a single 4,995,896-bp chromosome with 53.10% G + C content and harbors 4,306 predicted protein-coding genes. We estimated in silico DNA-DNA hybridization and average nucleotide identity values in combination with the whole-genome-based phylogeny from 19 Pectobacterium strains including P. aroidearum L6. The results showed that L6 and PC1 formed a population distinct from other populations of the Pectobacterium genus. Phylogenetic analysis based on 16S rRNA and genome sequences showed a close evolutionary relationship among Pectobacterium species. Overall, evolutionary analysis showed that L6 was in the same branch with PC1. In comparison with 18 Pectobacterium spp. reference pathogens, strain L6 had 2,712 gene families, among which 1,632 gene families were identified as orthologous to those strains, as well as 1 putative unique gene family. We discovered 478 genes, 10.4% of the total of predicted genes, that were potentially related to pathogenesis using the Virulence Factors of Pathogenic Bacteria database. A total of 25 genes were related to toxins, 35 encoded plant cell-wall degrading enzymes, and 122 were involved in secretion systems. This study provides a foundation for a better understanding of the genomic structure of P. aroidearum and particularly offers information for the discovery of potential pathogenic factors and the development of more effective strategies against this pathogen.


Is Cupressus sempervirens native in Italy? An answer from genetic and palaeobotanical data.
This study represents the first large-scale analysis using nuclear molecular markers to assess genetic diversity and structure of Cupressus sempervirens L.. Genetic and fossil data were combined to infer the possible role of human activity and evolutionary history in shaping the diversity of cypress populations. We analysed 30 populations with six polymorphic nuclear microsatellite markers. Dramatic reductions in heterozygosity and allelic richness were observed from east to west across the species range. Structure analysis assigned individuals to two main groups separating central Mediterranean and eastern populations. The two main groups could be further divided into five subgroups which showed the following geographical distributions: Turkey with the Greek islands Rhodes and Samos, Greece (Crete), Southern Italy, Northern Italy, Tunisia with Central Italy. This pattern of genetic structure is also supported by SAMOVA and Barrier analyses. Palaeobotanical data indicated that Cupressus was present in Italy in the Pliocene, Pleistocene and Holocene. Furthermore, our molecular survey showed that Italian cypress populations experienced bottlenecks that resulted in reduced genetic diversity and allelic richness and greater genetic differentiation. Recent colonization or introduction may also have influenced levels of diversity detected in the Italian populations, as most individuals found in this range today have multilocus genotypes that are also present in the eastern range of the species. The data reveal a new interpretation of the history of cypress distribution characterized by ancient eastern populations (Turkey and Greek islands) and a mosaic of recently introduced trees and remnants of ancient, depauperate populations in the central Mediterranean range.


Viperin interaction with mitochondrial antiviral signaling protein (MAVS) limits viperin-mediated inhibition of the interferon response in macrophages.
Viperin is an antiviral protein that is upregulated by interferons and by ligands for a variety of innate immune receptors. It possesses diverse capabilities and functions in an array of viral infections. Studies have shown that it appears to be particularly important in defence against RNA viruses, such as West Nile, Dengue, and Chikungunya viruses, although the specific mechanisms involved are not well understood at the molecular level. Here we identify the mitochondrial antiviral signalling protein MAVS as a novel viperin interaction partner, most likely in mitochondria associated membranes, and characterize a more central, overarching role of viperin as a negative regulator of the interferon response, an ability that can be regulated by the viperin-MAVS interaction. This suggests a novel mechanism of viperin action in immune defence against RNA viruses by which it may prevent pathology from excessive immune responses.


Osteoporotic vertebral compression fractures: surgery versus non-operative management.
This 12-month retrospective study compared pain relief, quality of life (QoL), treatment cost-effectiveness and complication rates in patients with acute osteoporotic vertebral compression fracture (OVCF) undergoing percutaneous vertebroplasty (PVP; n = 58), percutaneous kyphoplasty (PKP; n = 55), or conservative medical therapy (CMT; n = 55). After surgery, Cobb angle and vertebral height were significantly improved in the PKP group. PVP and PKP patients had significantly less pain immediately after surgery than CMT patients, but this difference disappeared between weeks 2-8, only to return from months 6-12. QoL was significantly better among the surgical groups after surgery and was lower in the CMT group than in the surgical groups. Treatment times were shorter with PVP and PKP, but costs were lower with CMT. The rate of secondary fractures during follow-up was greater with CMT. Overall, PVP was considered the first choice treatment for OVCF with refractory pain.


Molecular screening for fragile X syndrome in Thailand.
Fragile X syndrome (FXS) is the most common form of inherited mental retardation. We screened for FXS in 237 Thai males (age < or = 15 years) with developmental delay of unknown cause. We found 16 (6.8%) to have FXS using standard molecular analysis. Wc then studied the extended families of these 16 FXS subjects and 4 other independently ascertained FXS cases. We found that there were at least 35 affected males and 8 affected females. In addition we found that there were at least 31 premutation carrier females and 4 premutation males. The CGG repeats numbers in these premutation individuals ranged from 60 to 125. By comparison, the normal CGG repeats were 19-50 with a heterozygosity of 67.2% in 337 randomly selected males. This study providcs insight into the high incidence of FXS in developmentally delayed Thai males and points the way toward the means of prevention of mental retardation by genetic counseling and prenatal diagnosis.


A pilot study on ecological momentary assessment in asylum-seeking children and adolescents resettled to Germany: Investigating compliance, post-migration factors, and the relation between daily mood, sleep patterns, and mental health.
Asylum-seeking children and adolescents (ASCs) resettled to western countries show elevated levels of psychological distress. While research on the mental health of ASCs is increasing, less is known about their day-to-day living experiences such as their daily mood, sleep patterns, and post-migration factors. Moreover, no examination in situ, using smartphone-assisted ecological momentary assessment (EMA), has been conducted up to now among ASCs. Furthermore, we do not know if screening measures succeed in reflecting the daily mood of ASCs experienced in everyday life. We undertook a smartphone-assisted EMA study over a two-week period with 3 measurements a day. Participants were N = 40 ASCs from 10 different countries who had resettled to Germany. They completed standardized questionnaires screening for history of trauma and clinical symptoms (post-traumatic stress symptoms, depression, and anxiety) that were carried out in interview-like settings, and they participated in the subsequent EMA where they rated mood, sleep parameters, and post-migration factors on a daily basis. Multilevel models of clinical symptoms, daily mood, and sleep parameters were computed based on a total of 680 measurements. The multiply traumatized and highly distressed participants reported different levels of discrimination, and various social activities and contacts in the EMA. The overall compliance rate was shown to be 40.5%. Higher PTSS and anxiety scores were associated with lower levels of daily mood and poorer outcomes of some sleep parameters. Depression scores were not associated with any of the variables assessed in the EMA. Smartphone-assisted EMA among ASCs resettled to Germany proved to be implementable despite a rather low compliance rate. Not only do ASCs show high symptom levels, they are also affected by these symptoms in their daily lives. The results emphasize the need for concise screenings and psychological treatment for this high-risk population. Limitations include the convenient nature of the sample and the lack of a comparison group.


Early onset of severe lymphopenia during definitive radiotherapy correlates with mean body dose and predicts poor survival in cervical cancer.
Lymphopenia during definitive radiotherapy (RT) has been shown to reduce survival in patients with cervical cancer. However, there are few studies on the significance of onset time of lymphopenia during RT in patients with cervical cancer. This study aimed to exam the prognostic significance of early onset of severe lymphopenia (EOSL) during definitive RT in patients with cervical cancer. Newly diagnosed cervical cancer patients treated with definitive RT from January 2015 to December 2019 were eligible for this retrospective study. EOSL was defined as first onset of grade 3-4 lymphopenia ⩽ 3 weeks from the start of RT. Mean body dose (MBD) was the mean radiation dose absorbed by the body during the whole course of external beam RT (EBRT) and was directly obtained from the dose volume histogram (DVH) of the EBRT planning. Logistic regression analysis and restricted cubic spline (RCS) models were applied to assess relationships between clinicopathological factors and EOSL. Survival analysis was performed using Kaplan-Meier curves and log-rank test. A COX regression model was developed to predict overall survival (OS). A total of 104 patients were included and 59.6% had EOSL. MBD (P= 0.04), concurrent cisplatin (P= 0.011), and pre-RT absolute lymphocyte count (ALC) (P= 0.001) were associated with EOSL. A linear relationship (P for non-linearity = 0.803) between MBD and risk of EOSL was found. Patients with EOSL had decreased OS (2-yr 75.1% vs 91.1%, P= 0.021) and progression-free survival (PFS) (2-yr 71.2% vs 83.7%, P= 0.071). An OS prediction COX model was developed with C-index of 0.835 and AUC of 0.872. EOSL during definitive RT correlates with MBD and predicts poor survival in patients with cervical cancer.


The effects of medication use in transcranial direct current stimulation: A brief review.
There has been increased interest in the potential use of transcranial direct current stimulation (tDCS) as treatment for multiple conditions including depression, pain, and cognitive impairment. However, few studies account for the possible influence of comorbid medications when conducting tDCS research. This literature review was conducted to examine what is currently known about the impact of medications on tDCS, provide recommendations for future research practices, and highlight areas where more research is needed. Key terms were searched in PubMed and Web of Science to identify studies that examine the impact of medication on tDCS effects in adults. Relevant papers' reference lists were also reviewed for thoroughness. Studies examined the effects of medication on 1 mA tDCS delivered to M1 (motor) and orbit/supraorbital (SO) area. All studies measured the effects of tDCS via MEP TMS paradigm. Results of the literature review suggest multiple classes of medications, including sodium and calcium channel blockers, and medications that influence various neurotransmitter systems (GABA, dopamine, serotonin, etc.) may all impact tDCS effects on tissue excitability. Research to date suggests multiple classes of medications may impact tDCS effects. These results highlight the importance of documenting medication use in research subjects and carefully considering what types of medications should be allowed into tDCS trials. Many questions still remain regarding the exact mechanisms of action for tDCS and how various parameters (medication dosages, tDCS stimulation intensity, etc.) may further impact the effects of medications on tDCS.


Evaluating rapid participatory rural appraisal as an assessment of ethnoecological knowledge and local biodiversity patterns.
There is a pressing need to find both locally and globally relevant tools to measure and compare biodiversity patterns. Traditional ecological knowledge (TEK) is important to biodiversity monitoring, but has a contested role in preliminary biodiversity assessments. We examined rapid participatory rural appraisal (rPRA) (a tool commonly used for local needs assessments) as an alternative to surveys of vascular plants conducted by people with local knowledge. We used rPRA to determine the local-knowledge consensus on the average richness, diversity, and height of local grasses and trees in three habitats surrounding Boumba, Niger, bordering Park-W. We then conducted our own vascular plant surveys to collect information on plant richness, abundance, and structure. Using a qualitative ranking, we compared TEK-based assessments of diversity patterns with our survey-based assessments. The TEK-based assessments matched survey-based assessments on measures of height and density for grasses and trees and tree richness. The two assessments correlated poorly on herb richness and Simpson's D value for both trees and grasses. Plant life form and gender of the participant affected the way diversity patterns were described, which highlights the usefulness of TEK in explaining local realities and indicates limitations of using TEK as a large-scale assessment tool. Our results demonstrate that rPRA can serve to combine local-knowledge inquiry with scientific study at a cost lower than vascular plant surveys and demonstrates a useful blunt tool for preliminary biodiversity assessment.


Infection Prevalence and Antibiotic Resistance Levels in Ureaplasma urealyticum and Mycoplasma hominis in Gynecological Outpatients of a Tertiary Hospital in China from 2015 to 2018.
The aim of this study was to estimate the Ureaplasma urealyticum and Mycoplasma hominis infection prevalence and antibiotic resistance levels in gynecological outpatients. Clinical characteristics and laboratory data of gynecological outpatients of the Fourth People's Hospital of Chongqing from 2015 to 2018 were retrospectively analyzed. Antibiotic resistance levels in U. urealyticum and M. hominis were defined by a commercial Mycoplasma kit for antibiotic susceptibility testing. Univariate analysis and multivariate logistic regression analysis were performed to evaluate risk factors associated with Mycoplasma isolation. Comparisons of yearly distributions and resistance rates were assessed by chi-square tests. Fifty-six percent of gynecological outpatients were positive for U. urealyticum, and 11.02% were positive for M. hominis. In the univariate analysis, women aged 30-39 years or with a history of pregnancy or gynecological diseases had an increased risk for Mycoplasma isolation, while women who were postmenopausal or had an education level of undergraduate degree or above had a decreased risk of Mycoplasma isolation. In the multivariate logistic regression model, an independent risk factor for Mycoplasma isolation was a history of gynecological diseases, while a bachelor's degree, master's degree, or above were protective factors against Mycoplasma isolation. There were distinctly gradual increases in the positivity rates of U. urealyticum and M. hominis from 2015 to 2018 and an overall increasing trend of resistance to ten antibiotics among U. urealyticum and M. hominis. The top three antibiotics associated with resistance were ofloxacin, sparfloxacin, and levofloxacin. Doxycycline, josamycin, and minocycline were preferred because they had the lowest levels of resistance. Increases in the prevalence of infection and antibiotic resistance in U. urealyticum and M. hominis were observed from 2015 to 2018, clearly confirming the necessity to monitor the standardized administration of antibiotics.


Resonance Raman spectroscopic evidence for an anionic flavin semiquinone in bovine liver monoamine oxidase.
The flavoprotein monoamine oxidase B (MAO B) from bovine liver, as isolated, has an unusual additional absorption band at 412 nm, which is similar to the absorption of its anionic flavin semiquinone form, (Fl.-), and other typical (Fl.-) flavoproteins. Denaturation of the enzyme results in the elimination of this anomalous absorption. The resonance Raman (RR) spectrum of MAO B as isolated is virtually identical to that of its dithionite-reduced (Fl.-) form. Both spectra show features similar to those of the RR spectrum of the (Fl.-) form of Aspergillus niger glucose oxidase (GO) in the region between 300 and 1700 cm-1 with 406.7 nm excitation. These features are readily distinguishable from those of oxidized flavin, neutral flavin semiquinone, and hemoprotein, strongly suggesting the presence of an (Fl.-) form in MAO B as isolated, even with preparations isolated in the absence of light. There are significant differences between the RR spectra of the (Fl.-) form of MAO B and those of GO or the published RR spectra of the (Fl.-) form of D-amino acid oxidase with excess substrate analog. At least some of these differences can be attributed to the different binding of flavin in the three enzymes. No EPR signals due to (Fl.-) are observed in MAO B as isolated. The dithionite-reduced (Fl.-) form exhibits approximately 50% less EPR signal than that expected from the absorption spectrum, which suggests a possible coupling of the (Fl.-) flavin with a paramagnetic center of unknown identity in the protein. The implications of these observations on MAO B with the current view of its catalytic mechanism are discussed.


Development of a novel rat model of lumbar facet joint osteoarthritis induced by persistent compressive injury.
The aim of the present study was to develop a novel animal model of lumbar facet joint osteoarthritis induced by persistent compressive injury. An intraspinal compression spring was randomly implanted into either the L4/5 or the L5/6 spinal segments of 40 Sprague Dawley (SD) rats to induce compression. Sham-operations were used in the other segment of the same rats as the control levels. The animals were sacrificed at 7, 14, 28, 42 and 56 days after surgery, prior to the radiological confirmation of the spring location. Degeneration of the lumbar facet joints was evaluated by macroscopic observation in addition to histological and immunohistological analyses. The results of this present study revealed the absence of spring dislocation during the entire observation period. Macroscopic and Osteoarthritis Research Society International scores of the compression levels were found to be higher in the compression levels compared with those noted in the control levels (P<0.05). In addition, interleukin-1β and tumor necrosis factor-α expression in the compression levels were increased over time compared with those recorded in the control levels. In conclusion, persistent compressive injury may induce degeneration of the lumbar facet joint. This novel animal model could serve as a useful tool for further studies into the mechanisms of action and potential treatment of lumbar facet joint osteoarthritis.


Interleukin-17 contributes to Ross River virus-induced arthritis and myositis.
Arthritogenic alphaviruses are mosquito-borne viruses that are a major cause of infectious arthropathies worldwide, and recent outbreaks of chikungunya virus and Ross River virus (RRV) infections highlight the need for robust intervention strategies. Alphaviral arthritis can persist for months after the initial acute disease, and is mediated by cellular immune responses. A common strategy to limit inflammation and pathology is to dampen the overwhelming inflammatory responses by modulating proinflammatory cytokine pathways. Here, we investigate the contribution of interleukin-17 (IL-17), a cytokine involved in arthropathies such as rheumatoid arthritis, in the development RRV-induced arthritis and myositis. IL-17 was quantified in serum from RRV-infected patients, and mice were infected with RRV and joints and muscle tissues collected to analyse cellular infiltrates, tissue mRNA, cytokine expression, and joint and muscle histopathology. IL-17 expression was increased in musculoskeletal tissues and serum of RRV-infected mice and humans, respectively. IL-17-producing T cells and neutrophils contributed to the cellular infiltrate in the joint and muscle tissue during acute RRV disease in mice. Blockade of IL-17A/F using a monoclonal antibody (mAb) reduced disease severity in RRV-infected mice and led to decreased proinflammatory proteins, cellular infiltration in synovial tissues and cartilage damage, without affecting viral titers in inflamed tissues. IL-17A/F blockade triggered a shift in transcriptional profile of both leukocyte infiltrates and musculoskeletal stromal cells by downregulating proinflammatory genes. This study highlights a previously uncharacterized role for an effector cytokine in alphaviral pathology and points towards potential therapeutic benefit in targeting IL-17 to treat patients presenting with RRV-induced arthropathy.


UV-induced formation of pyrimidine dimers in nucleosome core DNA is strongly modulated with a period of 10.3 bases.
We have determined the distribution of the major UV-induced photoproducts in nucleosome core DNA using the 3'----5' exonuclease activity of T4 DNA polymerase, which has been shown to stop digestion immediately 3' to UV-induced pyrimidine dimers. This assay is extremely sensitive since all DNA fragments without photoproducts (background) are reduced to small oligonucleotides, which can be separated from those fragments containing photoproducts. The results show that the distribution of UV-induced photoproducts (primarily cyclobutane dipyrimidines) is not uniform throughout core DNA but displays a striking 10.3 (+/- 0.1) base periodicity. Furthermore, this characteristic distribution of photoproducts was obtained regardless of whether nucleosome core DNA was isolated from UV-irradiated intact chromatin fibers, histone H1-depleted chromatin fibers, isolated mononucleosomes, or cells in culture. The yield of pyrimidine dimers along the DNA seems to be modulated in a manner that reflects structural features of the nucleosome unit, possibly core histone-DNA interactions, since this pattern was not obtained for UV-irradiated core DNA either free in solution or bound tightly to calcium phosphate crystals. Based on their location relative to DNase I cutting sites, the sites of maximum pyrimidine dimer formation in core DNA mapped to positions where the phosphate backbone is farthest from the core histone surface. These results indicate that within the core region of nucleosomes, histone-DNA interactions significantly alter the quantum yield of cyclobutane dipyrimidines, possibly by restraining conformational changes in the DNA helix required for formation of these photoproducts.


Nonidentical function of Upc2A binding sites in the Candida glabrata CDR1 promoter.
Increased expression of the Candida glabrata CDR1 gene, encoding an ATP-binding cassette membrane transporter, is routinely observed in fluconazole-resistant isolates of this pathogenic yeast. CDR1 transcription has been well-documented to be due to activity of the Zn2Cys6 zinc cluster-containing transcription factor Pdr1. Gain-of-function mutations in the gene encoding this factor are the most commonly observed cause of fluconazole hyper-resistance in clinical isolates. We have recently found that the sterol-responsive transcription factor Upc2A also acts to control CDR1 transcription, providing a direct link between ergosterol biosynthesis and expression of Pdr1 target genes. While this earlier work implicated Upc2A as an activator of CDR1 transcription, our further analyses revealed the presence of a second Upc2A binding site that negatively regulated CDR1 expression. This Upc2A binding site designated a sterol-responsive element (SRE) was found to have significant lower affinity for Upc2A DNA-binding than the previously described SRE. This new SRE was designated SRE2 while the original, positively acting site was named SRE1. A mutant version of SRE2 prevented in vitro DNA-binding by recombinant Upc2A and, when introduced into the CDR1 promoter, caused decreased fluconazole susceptibility and increased CDR1 expression. This negative effect caused by loss of SRE2 was shown to be Pdr1 independent, consistent with the presence of at least one additional activator of CDR1 transcription. The ability of Upc2A to exert either positive or negative effects on gene expression resembles behavior of mammalian nuclear receptor proteins and reveals an unexpectedly complex nature for SRE effects on gene regulation.


Inspiratory muscle training in the patient with neuromuscular disease.
Pulmonary complications due to respiratory muscle dysfunction are commonly a source of morbidity and mortality in patients with neuromuscular diseases. This review discusses the adverse effects of respiratory muscle weakness on pulmonary mechanics and examines the role that inspiratory muscle training may play in reversing pulmonary dysfunction in these individuals. In asymptomatic persons, it is well established that the inspiratory muscles can be trained to increase both force and endurance. In patients with neuromuscular diseases, the effects of training protocols on force and endurance are more controversial. This article reviews seven studies that have evaluated respiratory muscle training in a total of 75 patients with varied neuromuscular disorders. Training regimens included breathing through inspiratory resistive loads and isocapnic hyperpnea. Despite methodologic differences among studies, investigators have generally shown that the inspiratory muscles are similar to other skeletal muscle groups in that they can be trained for both force and endurance in these patients. The training-related improvements in inspiratory muscle performance are more pronounced in patients who are less severely affected by their disease. In those patients who have disease to the extent that they are already retaining carbon dioxide, there is little change in force or endurance with training. In these individuals, the inspiratory muscles may already be working at a level sufficiently severe to provide a training stimulus with each breath. No adverse effects of inspiratory muscle training were reported. Inspiratory muscle training can improve force and endurance in patients with neuromuscular weakness.(ABSTRACT TRUNCATED AT 250 WORDS)


Fluorine Scan of Inhibitors of the Cysteine Protease Human Cathepsin L: Dipolar and Quadrupolar Effects in the π-Stacking of Fluorinated Phenyl Rings on Peptide Amide Bonds.
The π-stacking of fluorinated benzene rings on protein backbone amide groups was investigated, using a dual approach comprising enzyme-ligand binding studies complemented by high-level quantum chemical calculations. In the experimental study, the phenyl substituent of triazine nitrile inhibitors of human cathepsin L (hCatL), which stacks onto the peptide amide bond Gly67-Gly68 at the entrance of the S3 pocket, was systematically fluorinated, and differences in inhibitory potency were measured in a fluorimetric assay. Binding affinity is influenced by lipophilicity (clog P), the dipole and quadrupole moments of the fluorinated rings, but also by additional interactions of the introduced fluorine atoms with the local environment of the pocket. Generally, the higher the degree of fluorination, the better the binding affinities. Gas phase calculations strongly support the contributions of the molecular quadrupole moments of the fluorinated phenyl rings to the π-stacking interaction with the peptide bond. These findings provide useful guidelines for enhancing π-stacking on protein amide fragments.


Structural and physicochemical characteristics of novel basic proteins isolated from duck egg white.
Novel basic proteins, duck basic protein small 1 (dBPS(1)) and 2 (dBPS(2)), were isolated from duck egg white by cation-exchange and gel filtration chromatography. Protein sequence analyses indicated that they possessed 39 amino acid residues with three disulfide bonds. The amino acid sequence of dBPS(1) showed 45% identity with dBPS(2). The amino acid sequence of dBPS(2) was the same as cygnin, a small protein from black swan, and strongly homologous with meleagrin from turkey and chicken. Phylogenic relationships implied that dBPS(1) and dBPS(2) share a common ancestry with cygnin and meleagrin. Based on MALDI-TOF mass spectra, the molecular masses of dBPS(1) and dBPS(2) were 4,373, and the 4,486 Da. pI of dBPS(1) and dBPS(2) elucidated by isoelectric focusing were 9.35 and 9.44. FT-IR spectra classified these proteins as (beta) proteins. Both dBPS(1) and dBPS(2), possessed high heat stability, Td 101.2 and 98.3 degrees C. Indirect ELISA results showed that the dBPS(1)/dBPS(2)-related proteins were distributed in the oviduct and gallbladder.


[Evidence-based clinical practice guidelines (CPGs) in oral care 1. Societal-, professional- and care-related perspective].
Some decades ago the need for clinical decision-making based on the best available evidence, and in that way providing accountability for professional services to society, was emerging in health care. The main purpose was to translate innovative knowledge from reliable resources into clinical practice to prevent inappropriate and unsafe care. In oral care it is also diserable to carry out improvements and to make treatment decisions more transparent. Evidence-based decision-making is not self-evident, and the development and the use of evidence-based clinical practice guidelines are in their infancy. Recently, national agreement has been reached among professional associations, scientific societies and educational institutions regarding the content of a national structure for the development of evidence-based guidelines within an independent institute for knowledge translation (KiMo).


Paraquat modulates immunological function in bone marrow-derived macrophages.
The herbicide paraquat (PQ) is known to affect the immune system. Many reports have indicated that PQ impacts on the viability and functions of the immune cells, however, the underlying mechanism in detail is still unknown. The aim of this study was to evaluate the effects of PQ on the free radical production, oxidative stress, cell death and pro-inflammatory gene expression of murine bone marrow-derived macrophages (BMDMs) from C57BL/6NJcl mice in vitro. BMDMs were incubated with PQ at 0, 200 and 400 µM concentrations for 24 h. Intracellular reactive oxygen species (ROS) production, apoptosis, cell viability, nitric oxide, inducible nitric oxide synthase (iNOS), and IL-6 expression levels were measured. The results revealed that PQ treatments led to a decrease in the cell viability and induced apoptotic cell death in a dose-dependent manner. Additionally, PQ also induced the generation of ROS. The mRNA level of the pro-inflammatory mediator genes iNOS and IL-6 were also elevated, while the level of lipid peroxide (malondialdehyde) production remained unaltered. Interestingly, the PQ treatment led to a decrease in the nitric oxide production. These results indicate that the increased cellular ROS production, due to the PQ treatment, induces apoptosis and the herbicide triggers production of iNOS and IL-6 in BMDMs.


Utility of Repeat Head Computed Tomography for Intracranial Hemorrhage After Trauma and Importance of Direct Patient Care.
At many institutions, it is common practice for trauma patients with traumatic intracranial hemorrhage (ICH) to receive routine repeat head computed tomographic (CT) scans after the initial CT scan, regardless of symptoms, to evaluate progression of the injury. The purpose of this study was to assess quantifiable risk factors (age, anticoagulation, gender) that could place patients at greater risk for progression of injury, thus requiring surgical intervention (craniotomy, craniectomy) for which serial CT scanning would be useful. From January 2014 to June 2015, a total of 211 patients presented with traumatic ICH and 198 were eligible for inclusion. Twenty-six patients required operative intervention for ICH. One of 26 patients went to the operating room as a result of repeat head CT scans without associated mental status change, change in neurological examination, or associated symptoms such as nausea or vomiting. Significant changes in patient management due to routine repeat CT scans were not observed. There were no statistically significant risk factors identified to place patients at higher risk for progression of disease. The data from this analysis emphasized the importance of nursing care in identifying and relaying changes in patient condition to the trauma team.


An interdisciplinary approach for surgical treatment of the renal mass.
Recent trends in surgery for the renal mass indicate that the type of surgery performed may depend largely on surgeon practice style. Since 2004 we have used an interdisciplinary approach for the surgical treatment of the renal mass. We report the results of this practice including oncologic and surgical outcomes. A prospective database of patients undergoing treatment for renal mass was analyzed. Minimally invasive surgery (MIS) was performed by a laparoscopist, and open surgery was performed by a urologic oncologist. Demographic and clinicopathologic data were compared between treatment groups using nonparametric analysis of variance. Of 120 patients treated for renal mass, 34% were treated after internal referral, 34% with nephron sparing surgery (NSS), 68% with MIS, and 32% with open surgery. Internal referrals accounted for 77% of patients who underwent open partial nephrectomy (OPN), 32% who underwent open radical nephrectomy (ORN), and 26% who underwent MIS. There were no significant differences in gender, mean ASA, or smoking history between groups. Patients in the ORN group were more likely symptomatic (P<0.001). Patients undergoing ORN or LRN had larger tumors than those undergoing open or laparoscopic partial nephrectomy (OPN and LPN) (P<0.001). Tumor stage, grade, and positive margin rate were highest in the ORN group (P<0.001). Hospital stay was shortest in the MIS and NSS groups (P<0.001). Complications were not different between groups. An interdisciplinary approach to the treatment of renal mass involving both a laparoscopist and urologic oncologist may reduce the impact of surgeon practice style on the type of surgery performed.


Cricothyroidotomy: a decade of experience in Denver.
In an attempt to evaluate cricothyroidotomy as described by Brantigan and Grow in 1976, the authors have reviewed the literature and compared it to the decade of experience following Brantigan and Grow's report. The records of over 1,000 patients requiring ventilatory assistance were reviewed. A comparison of this experience with Brantigan and Grow's original series and subsequent reports was used to establish the criteria and technique for cricothyroidotomy. It appears that while cricothyroidotomy has specific advantages, it also has disadvantages and a higher incidence of airway stenosis than either of the procedures it was designed to replace (low tracheotomy or endotracheal intubation). For this reason, its use has been severely restricted in Colorado, where it was popularized.


MicroRNA‑224 is downregulated in mucinous cystic neoplasms of the pancreas and may regulate tumorigenesis by targeting Jagged1.
The underlying malignancy of mucinous cystic neoplasms (MCNs) of the pancreas most commonly results in patients undergoing surgery. The tumorigenesis of MCNs remains elusive and few studies have investigated the role of specific micro (mi)RNAs in MCNs. The present study focused on the expression of miRNA‑224 and its putative target gene Jagged1 (Jag1) to examine its role in tumorigenesis and its suitability as a biomarker for MCNs. Paired tissue samples confirmed by surgical pathology were used to screen the miRNAs involved in MCNs with miRNA microarrays (n=3), and to verify the differentially expressed miRNAs (n=3) and mRNAs of candidate target genes of miRNAs by quantitative polymerase chain reaction (qPCR; n=8). Immunohistochemistry was conducted to confirm the expression and location of Jag1 in the neoplastic epithelial cells. Luciferase assays were performed to confirm the direct target gene of miRNA‑224. miRNA microarray analysis revealed that two differentially expressed miRNAs were closely associated with tumorigenesis and pancreatic diseases. The qPCR results revealed that miRNA‑224 was more significantly aberrantly expressed and the mRNA expression levels of its putative target gene, Jag1, were upregulated. Strong, diffuse cytoplasmic immunohistochemical labeling of Jag1 with occasional nuclear labeling was detected in the mucinous epithelium. Luciferase reporter activity was significantly reduced by co‑transfected miRNA‑224 mimics and pMIR‑Jag1‑wild-type, which suggested that miRNA‑224 bound to recognition sites in the 3' untranslated region of its target mRNA, Jag1. In conclusion, miRNA‑224 was downregulated in MCNs and may regulate tumorigenesis by targeting Jag1. Further studies investigating the role of miRNAs and functional analysis of epigenetic alterations are required to examine the diagnostic and therapeutic potential of miRNAs in MCNs.


Beneficial effects of lexipafant, a PAF antagonist on gut barrier dysfunction caused by intestinal ischemia and reperfusion in rats.
Platelet-activating factor (PAF) may play a pivotal role in the pathogenesis of intestinal ischemic injury. The potential role of PAF in intestinal ischemia and reperfusion (I/R) and the development of gut endothelial and epithelial barrier dysfunction and distant organ injury were investigated by pretreatment with a PAF antagonist, lexipafant. Bidirectional permeability of the intestinal barrier, enteric bacterial translocation, protease-antiprotease balance and mucosal histology, and also changes in pulmonary and liver endothelial barrier permeability were measured following intestinal ischemia for 40 min with 6 h of reperfusion in rats. Intestinal mucosal endothelial and epithelial permeabilities significantly increased in animals with I/R. Lexipafant prevented the increase in albumin leakage from blood to the mucosal interstitium and the intestinal lumen during reperfusion, and the mucosal albumin leakage from the gut lumen to blood during I/R. Bacterial translocation was frequently noted in animals with I/R, while only a few positive cultures were obtained in animals with I/R administered lexipafant. Less leakage of fluorescein isothiocyanate dextran 70,000 into the interstitial space and gut lumen in I/R animals with lexipafant pretreatment was found under fluorescein microscopy. Lexipafant also partly prevented C1 inhibitor, prekallikrein, and factor X consumption in I/R animals and partly prevented changes in pulmonary and liver albumin leakage. PAF seems to play an important role in I/R-associated intestinal dysfunction and the development of distant organ dysfunction, probably by triggering endothelial and epithelial barrier dysfunction. Furthermore, PAF seems to be partly involved in activation of the protease-antiprotease system. The use of PAF antagonists may provide a mode of treatment against I/R-associated organ dysfunction.


[Lumbar interbody fusion with threaded titanium cages. Results on 222 cases].
Retrospective analysis of 222 cases of degenerative disc disease treated by threaded cage fusion. The objective was to determine the safety and efficiency of lumbar interbody fusions using screwed titanium cages and autogenous bone. Two hundred twenty-two patients had lumbar fusion at 243 levels between L2 and S1, at one or two disc spaces. Main indication was discogenic back pain with radicular leg radiation in degenerative discopathy complicated by disc protusion, segmental canal stenosis with chronic instability or spondylolysthesis of the first degree. Previous failed surgery after discectomy, nonunion or biologically cured discitis were other indications in selected cases. Results were classified as good to excellent in 80%, 15% improved but remained disabled, 5% had minimal or no improvement. Fusion rate was 91% at one year and 96% at 2 years. Peroperative dural tears occurred in 10 patients and transient neurological deficits in 9. A superficial infection occurred in one patient. Reoperation in the first three months included a cage revision in one patient and a foraminotomy in another. Two osteoporotic women needed an additional posterior fixation for kyphotic deformity. In conclusion, lumbar interbody fusion with threaded titanium cages appears to be efficacious with an acceptable rate of complications. Experience up to 7 years confirms that impression. Long term observation is needed before recommending this new method.


Modulation of Bi2 MoO6 -Based Materials for Photocatalytic Water Splitting and Environmental Application: a Critical Review.
Highly active photocatalysts driving chemical reactions are of paramount importance toward renewable energy substitutes and environmental protection. As a fascinating Aurivillius phase material, Bi2 MoO6 has been the hotspot in photocatalytic applications due to its visible light absorption, nontoxicity, low cost, and high chemical durability. However, pure Bi2 MoO6 suffers from low efficiency in separating photogenerated carriers, small surface area, and poor quantum yield, resulting in low photocatalytic activity. Various strategies, such as morphology control, doping/defect-introduction, metal deposition, semiconductor combination, and surface modification with conjugative π structures, have been systematically explored to improve the photocatalytic activity of Bi2 MoO6 . To accelerate further developments of Bi2 MoO6 in the field of photocatalysis, this comprehensive Review endeavors to summarize recent research progress for the construction of highly efficient Bi2 MoO6 -based photocatalysts. Furthermore, benefiting from the enhanced photocatalytic activity of Bi2 MoO6 -based materials, various photocatalytic applications including water splitting, pollutant removal, and disinfection of bacteria, were introduced and critically reviewed. Finally, the current challenges and prospects of Bi2 MoO6 are pointed out. This comprehensive Review is expected to consolidate the existing fundamental theories of photocatalysis and pave a novel avenue to rationally design highly efficient Bi2 MoO6 -based photocatalysts for environmental pollution control and green energy development.


"If I Am Straight You Are Askew": Labelling Heterosexuals as Straight Worsen Gay Men's Perception.
A robust stream of research has shown the detrimental influence of slurs and derogatory epithets on attitudes toward minority groups. Extending prior work, we explored the influence of positive labels ascribed to the majority group on the evaluation of the minority group. Specifically, three studies tested the possibility that the label "straight," generally linked with the concept of morality, would promote a negative evaluation of gay men. Study 1 exposed English speakers to an individual person described as straight (vs. heterosexual) while Study 2 exposed English speakers to a target person described as straight (vs. heterosexual vs. no label). Study 3 considered a non-English sample (i.e., Italian adults) and experimentally induced the association between the straight label and the concept of heterosexuality. In each study, participants were asked to express their attitudes toward a gay target after the manipulation. Results showed that heterosexual participants exposed to the label "straight" reported more negative attitudes toward gay men than heterosexual participants exposed to the label "heterosexual" (or when they were not exposed to any label). Critically, such an effect emerged only among highly religious participants. Implications for policies and prejudice reduction are discussed.


Comparative in vitro flow study of 3 different Ex-PRESS miniature glaucoma device models.
To determine the flow characteristics of the 3 different models of the Ex-PRESS miniature glaucoma device in a controlled laboratory study. The 3 different Ex-PRESS models (P-50, R-50, and P-200; Optonol Ltd; now Alcon Lab) were tested using a gravity-driven flow test. Three samples of each of the 3 Ex-PRESS models were subjected to a constant gravitational force of fluid at 5 different pressure levels (5 to 25 mm Hg). Four measurements per sample were taken at each pressure level. The main outcome measure was flow rate (Q) (µL/min). Resistance (R) was calculated by dividing pressure (P) by the measured flow (Q). The flow rate was primarily pressure dependent. The P-200 model (internal diameter 200 µm) showed a statistically significant higher flow rate and lower resistance compared with both the P-50 and R-50 models (internal diameter 50 µm) (P<0.0001). The P-50 and R-50 models demonstrated similar flow rates (P=0.08) despite their difference in tube length (2.64 vs. 2.94 mm). The 3 models of the Ex-PRESS mini shunt behaved in vitro as simple flow resistors by creating a relatively constant resistance to flow. Tube diameter was the only parameter with significant impact on flow and resistance. All models demonstrated flow rates per unit of pressure much higher than the outflow facility of a healthy human eye.


Silencing of the JNK pathway maintains progesterone receptor activity in decidualizing human endometrial stromal cells exposed to oxidative stress signals.
Survival of the conceptus is dependent on continuous progesterone signaling in the maternal decidua but how this is achieved under conditions of oxidative stress that characterize early pregnancy is unknown. Using primary cultures, we show that modest levels of reactive oxygen species (ROS) increase sumoylation in human endometrial stromal cells (HESCs), leading to enhanced modification and transcriptional inhibition of the progesterone receptor (PR). The ability of ROS to induce a sustained hypersumoylation response, or interfere with PR activity, was lost upon differentiation of HESCs into decidual cells. Hypersumoylation in response to modest levels of ROS requires activation of the JNK pathway. Although ROS-dependent JNK signaling is disabled on decidualization, the cells continue to mount a transcriptional response, albeit distinct from that observed in undifferentiated HESCs. We further show that attenuated JNK signaling in decidual cells is a direct consequence of altered expression of key pathway modulators, including induction of MAP kinase phosphatase 1 (MKP1). Overexpression of MKP1 dampens JNK signaling, prevents hypersumoylation, and maintains PR activity in undifferentiated HESCs exposed to ROS. Thus, JNK silencing uncouples ROS signaling from the SUMO conjugation pathway and maintains progesterone responses and cellular homeostasis in decidual cells under oxidative stress conditions imposed by pregnancy.


Amphiphilic Polymer-Based Fluorescent Probe for Enantioselective Recognition of Amino Acids in Immiscible Water and Organic Phases.
Atom transfer radical polymerization (ATRP) of N-isopropylacrylamide was conducted in the presence of a 3,3'-diformyl-1,1'-BINOL-based diinitiator (BINOL=1,1'-bi-2-naphthol) to give polymer (S)-7, which was soluble in both water and common organic solvents. Polymer (S)-7 in combination with Zn2+ in aqueous solution (BICINE buffer at pH 8.80) showed highly enantioselective fluorescence enhancement in the presence of a number of amino acids. It was found that chloroform can be used to extract the aqueous polymer-Zn2+ -amino acid solution and the resulting chloroform extract maintained the highly enantioselective fluorescence response. Thus, the enantiomeric composition of a chiral amino acid can be determined in the two immiscible solvents of water and chloroform. The aqueous polymer-Zn2+ -amino acid solution showed a lower critical solution temperature (LCST) at 34 °C, above which the polymer-Zn2+ -amino acid adduct precipitated out. Measuring the fluorescence of the precipitate redissolved in the aqueous buffer solution showed the retention of the high enantioselectivity. Both the chloroform extraction and the thermo-induced precipitation have allowed the fluorescence response of the sensor toward amino acids to be measured away from the original substrate solution. These two strategies should minimize the interference by other reaction components on the fluorescence measurement when the sensor is applied to analyze the asymmetric reaction screening experiments.


Comeback of the Rat in Biomedical Research.
Rats were the first mammalian species domesticated for scientific purposes, and they soon became the most widely used animal model in biomedical sciences, including cardiovascular research and behavioral neuroscience. Yet, after the development of technologies to manipulate genes, researchers largely shifted to the use of mice. However, as we lay out with examples from drug addiction, social behavior, and cardiovascular research, rats have experimental advantages over mice. With the introduction of zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) methodologies, and, specifically, the clustered regularly interspaced short palindromic repeats (CRISPR) associated system, gene targeting is no longer limited to mice. Development of genetic technologies in rats allows researchers to take advantage of the unique opportunities offered by this species in biomedical research.