Depression, anxiety, and suicidal ideation among Vietnamese secondary school students and proposed solutions: a cross-sectional study.
There is a rapidly growing public awareness of mental health problems among Vietnamese secondary school students. This study aims to determine the prevalence of anxiety, depression, and suicidal ideation, to identify related risk factors, and to explore students' own proposals for improving their mental health. A cross-sectional study was conducted among 1161 secondary students in Can Tho City, Vietnam during September through December, 2011. A structured questionnaire was used to assess anxiety, depression, suicidal ideation and proposed solutions. Depression was measured using the Center for Epidemiology Studies Depression Scale. The prevalence estimates of symptoms reaching a threshold comparable to a diagnosis of anxiety and depression were 22.8% and 41.1%, respectively. Suicide had been seriously considered by 26.3% of the students, while 12.9% had made a suicide plan and 3.8% had attempted suicide. Major risk factors related to anxiety and depression were physical or emotional abuse by the family, and high educational stress. As proposed solutions, nearly 80% of students suggested that the academic workload should be reduced and that confidential counselors should be appointed at schools. About half the students stated that the attitudes of their parents and teachers needed to change. A significant majority said that they would visit a website that provided mental health support for students. Anxiety, depression, and suicidal ideation are common among Vietnamese secondary school students. There are strong associations with physical and emotional abuse in the family and high educational stress. Academic curricula and attitudes of parents and teachers need to be changed from a punitive to a more supportive approach to reduce the risk of poor mental health. An internet-based mental health intervention could be a feasible and effective first step to improve students' mental health.


Implicit memory is independent from IQ and age but not from etiology: evidence from Down and Williams syndromes.
In the last few years, experimental data have been reported on differences in implicit memory processes of genetically distinct groups of individuals with Intellectual Disability (ID). These evidences are relevant for the more general debate on supposed asynchrony of cognitive maturation in children with abnormal brain development. This study, comparing implicit memory processes in individuals with Williams syndrome (WS) and Down syndrome (DS), was planned to verify the 'etiological specificity' hypotheses pertaining to the skill learning abilities of individuals with ID. A modified version of Nissen and Bullemer's (1987) Serial Reaction Time (SRT) task was used. The performances of three group were evaluated. The first group consisted of thirty-two people with WS (18 males and 14 females). The second group was comprised of twenty-six individuals with DS (14 males and 12 females). The two groups of individuals with ID were selected so that the groups were comparable as for mental age and chronological age. The third group consisted of forty-nine typically developed children with a mental age similar to that of the groups with WS and DS. The two groups of individuals with ID demonstrated different patterns of procedural learning. WS individuals revealed poor implicit learning of the temporal sequence of events characterizing the ordered blocks in the SRT task. Indeed, differently from normal controls, WS participants showed no reaction time (RT) speeding through ordered blocks. Most importantly, the rebound effect, which so dramatically affected normal children's RTs passing from the last ordered to the last block, had only a marginal influence on WS children's RTs. Differently from the WS group, the rate of procedural learning of the participants with DS was comparable to that of their controls. Indeed, DS and typically developed individuals showed parallel RT variations in the series of ordered blocks and, more importantly, passing from the last ordered to the last block. Therefore, a substantial preservation of skill learning abilities in this genetic syndrome is confirmed. The results of the present study document that procedural learning in individuals with ID depends on the aetiology of the syndrome, thus supporting the etiological specificity account of their cognitive development. These results are relevant for our knowledge about the qualitative aspects and the underlying neurobiological substrate of the anomalous cognitive development in mentally retarded people.


Asymmetries in mating preferences between species: female swordtails prefer heterospecific males.
In male swordtails ((Xiphophorus nigrensis)) there are three size classes that derive from allelic variation at the pituitary locus on the Y chromosome. Progeny analysis and preference tests suggest that females prefer to mate with larger males. In the closely related X. pygmaeus, there is no allelic variation at this locus; this species consists of males similar in size only to smaller X. nigrensis males. In addition to being smaller than most X. nigrensis males, these X.pygmaeus males also lack both the swordtail and a major component of the courtship display common in most X. nigrensis males. Usually, female X. pygmaeus prefer to mate with heterospecific males rather than conspecifics, regardless of body size and the presence of a swordtail. However, the smallest X. nigrensis males lack the same courtship component as do the X. pygmaeus males, and in this comparison female X. pygmaeus show no preference. Although sexual selection, through its action on divergence of courtship displays, has been implicated as a factor leading to speciation, in this case sexual selection could lead to the congealing of gene pools between heterospecifics.


[Hydatid cysts of the liver. Therapeutic and prognostic classification. 378 cases].
We retrospectively examined our clinical data on hydatic cysts of the liver collected over the last 10 years in order to determine a classification which could be used to guide future therapeutic decisions. From 1982 to 1992, hydatic cysts of the liver were surgically removed in 378 patients (mean age 38 +/- 12 years). Echography had been performed in all patients. Other preoperative investigations included computerized tomodensitometry (n = 57) and arteriography of the caeliomesenteric arteries (n = 12). Histological examination of surgical specimens included research for parasite inclusions within the pericyst and the hepatic parenchyma. Single cysts were found in 65.7% of the cases, double cysts in 20% and multiple cysts in 12.5%. Histology revealed parasites in the pericyst in 129 cases (34%) and a fistula from the cyst to the bile duct was observed in 47 cases (12.5%). A classification was obtained based on 5 criteria: localization and number of cysts, cyst content, morphology of the pericyst and biliary-cyst fistula. The excellent correlation between this classification and prognosis provides a valuable tool for the management of hepatic hydatic cysts.


Anxiety and depressive symptoms and anxiety sensitivity in youngsters with noncardiac chest pain and benign heart murmurs.
Chest pain in children and adolescents is rarely associated with cardiac disease. We sought to examine psychological symptoms in youngsters with medically unexplained chest pain. We hypothesized that children and adolescents with medically unexplained chest pain would have high rates of anxiety and depressive symptoms. We assessed 65 youngsters with noncardiac chest pain (NCCP) and 45 comparison youngsters with benign heart murmurs using self-report measures of anxiety and depressive symptoms and anxiety sensitivity. Compared with the asymptomatic benign-murmur group, youngsters with NCCP had higher levels of some anxiety symptoms and anxiety sensitivity. Differences on depressive symptoms were not significant. Though preliminary, results suggest that youngsters with chest pain may experience increased levels of some psychological symptoms. Future studies of noncardiac chest pain in youngsters should include larger samples and comprehensive diagnostic assessments as well as long-term follow-up evaluations.


Oligo-Fucoidan Improves Diabetes-Induced Renal Fibrosis via Activation of Sirt-1, GLP-1R, and Nrf2/HO-1: An In Vitro and In Vivo Study.
Fucoidan extracted from brown algae has multiple beneficial functions. In this study, we investigated the effects of low-molecular-weight fucoidan (oligo-FO) on renal fibrosis under in vitro and in vivo diabetic conditions, and its molecular mechanisms. Advanced glycation product (AGE)-stimulated rat renal proximal tubular epithelial cells (NRK-52E) and diabetic mice induced by high-fat diet and intraperitoneal injection of streptozotocin and nicotinamide were used. Oligo-FO treatment significantly inhibited anti-high mobility group box 1 (HMGB1)/RAGE/ anti-nuclear factor-kappa B (NF-κB)/transforming growth factor-β1 (TGF-β1)/TGF-β1R/Smad 2/3/fibronectin signaling pathway and HIF-1α activation in AGE-stimulated NRK-52E cells. Conversely, the expression and activity of Sirt-1; the levels of ubiquitin-specific peptidase 22 (USP22), p-AMPK, glucagon-like peptide-1 receptor (GLP-1R), and heme oxygenase-1 (HO-1); and Nrf2 activation were remarkably increased by oligo-FO in AGE-stimulated cells. However, the above effects of oligo-FO were greatly diminished by inhibiting Sirt-1, HO-1, or GLP-1R activity. Similar changes of these pro-fibrotic genes in the kidney and a marked attenuation of renal injury and dysfunction were observed in oligo-FO-treated diabetic mice. These findings indicated that the inhibitory effects of the oligo-FO on diabetes-evoked renal fibrosis are mediated by suppressing TGF-β1-activated pro-fibrogenic processes via Sirt-1, HO-1, and GLP-1R dependence. Collectively, fucoidan-containing foods or supplements may be potential agents for ameliorating renal diseases due to excessive fibrosis.


Understanding Estimations of Magnitudes: An fMRI Investigation.
The current study examined whether discrete numerical estimation is based on the same cognitive process as estimation of continuous magnitudes such as weight and time. While the verbal estimation of numerical quantities has a contingent unit of measurement (e.g., how many cookies fit in a cookie jar? _X_ cookies), estimation of time and weight does not (e.g., how much time does it take to fill a bath with water? _X_ minutes/hours/seconds). Therefore, estimation of the latter categories has another level of difficulty, requiring extensive involvement of cognitive control. During a functional magnetic resonance imaging (fMRI) scan, 18 students performed estimations with three estimation categories: number, time, and weight. Estimations elicited activity in multiple brain regions, mainly: (1) visual regions including bilateral lingual gyrus), (2) parietal regions including the left angular gyrus and right supramarginal gyrus, and (3) the frontal regions (cingulate gyrus and the inferior frontal cortex). Continuous magnitude estimations (mostly time) produced different frontal activity than discrete numerical estimations did, demonstrating different profiles of brain activations between discrete numerical estimations and estimations of continuous magnitudes. The activity level in the right middle and inferior frontal gyrus correlated with the tendency to give extreme responses, signifying the importance of the right prefrontal lobe in estimations.


Irisin exerts a therapeutic effect against myocardial infarction via promoting angiogenesis.
Irisin, a myokine, is cleaved from the extracellular portion of fibronectin domain-containing 5 protein in skeletal muscle and myocardium and secreted into circulation as a hormone during exercise. Irisin has been found to exert protective effects against lung and heart injuries. However, whether irisin influences myocardial infarction (MI) remains unclear. In this study we investigated the therapeutic effects of irisin in an acute MI model and its underlying mechanisms. Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery and treated with irisin for 2 weeks after MI. Cardiac function was assessed using echocardiography. We found that irisin administration significantly alleviated MI-induced cardiac dysfunction and ventricular dilation at 4 weeks post-MI. Irisin significantly reduced infarct size and fibrosis in post-MI hearts. Irisin administration significantly increased angiogenesis in the infarct border zone and decreased cardiomyocyte apoptosis, but did not influence cardiomyocyte proliferation. In human umbilical vein endothelial cells (HUVEC), irisin significantly increased the phosphorylation of ERK, and promoted the migration of HUVEC detected in wound-healing and transwell chamber migration assay. The effects of irisin were blocked by the ERK inhibitor U0126. In conclusion, irisin improves cardiac function and reduces infarct size in post-MI mouse heart. The therapeutic effect is associated with its pro-angiogenic function through activating ERK signaling pathway.


[Comparative evaluation of the levels of water-soluble glial fibrillary acidic protein in the human brain in the normal state and in schizophrenia].
The concentration of water-soluble glial fibrillary acidic protein was measured in several regions of human brains (12 schizophrenic patients and 13 patients without any signs of mental disease) using ELISA technique. The content of this protein was lower in thalamus and gyrus cinguli in schizophrenics as compared to normals (p less than 0.01). The protein showed no correlation with sex, age and the terms of autopsy (5 to 7 h after death). The findings suggest that decreasing concentration of the protein might reflect the changes of its synthesis, posttranslational modifications, assembling and disassembling of glial filaments and possibly the effect of psychotropic drugs.


Creatine supplementation elicits greater muscle hypertrophy in upper than lower limbs and trunk in resistance-trained men.
Creatine (Cr) supplementation associated with resistance training produces greater muscular strength improvements in the upper compared with the lower body; however, no study has investigated if such region-specific results are seen with gains in muscle mass. We aimed to evaluate the effect of Cr supplementation in combination with resistance training on lean soft tissue changes in the upper and lower limbs and trunk in resistance-trained young adult men. In a randomized, double-blind and placebo-controlled design, 43 resistance-trained men (22.7 ± 3.0 years, 72.9 ± 8.7 kg, 177.9 ± 5.7 cm, 23.0 ± 2.5 kg/m2) received either creatine (Cr, n = 22) or placebo (PLA, n = 21) over an 8-week study period. The supplementation protocol included a loading phase (7 days, four doses of 0.3 g/kg per day) and a maintenance phase (7 weeks, single dose of 0.03 g/kg per day). During the same period, subjects performed resistance training four times per week using the following two-way split routine: Monday and Thursday = pectoral, shoulders, triceps, and abdomen, Tuesday and Friday = back, biceps, thighs, and calves. Lean soft tissue of the upper limbs (ULLST), lower limbs (LLLST), and trunk (TLST) was assessed by dual-energy X-ray absorptiometry before and after the intervention. Both groups showed significant ( p < 0.001) improvements in ULLST, LLLST, TLST, and the Cr group achieved greater ( p < 0.001) increases in these outcomes compared with PLA. For the Cr group, improvements in ULLST (7.1 ± 2.9%) were higher than those observed in LLLST (3.2 ± 2.1%) and TLST (2.1 ± 2.2%). Otherwise, for PLA group there was no significant difference in the magnitude of segmental muscle hypertrophy (ULLST = 1.6 ± 3.0%; LLLST = 0.7 ± 2.8%; TLST = 0.7 ± 2.8%). Our results suggest that Cr supplementation can positively augment muscle hypertrophy in resistance-trained young adult men, particularly in the upper limbs.


Evaluation of a phenylalanine-free product for treatment of phenylketonuria.
Ten children with classic phenylketonuria (PKU) participated in a controlled study of a phenylalanine-free formula recently released in the United States (PKU-2). Control data were obtained in the clinic while the children were receiving their baseline formula. The children were given the study formula and returned to the clinic for follow-up after they had been receiving the new formula for 4, 8, and 12 months. Serum phenylalanine and tyrosine concentrations, other hematologic measurements, urine analysis, growth, electroencephalogram, and physical findings remained similar to baseline values throughout the study. Nutrient intakes were comparable with the exception of a decrease in several micronutrients relative to baseline levels. We found that PKU-2 is appropriate for children with PKU who are over 3 years of age and may prove beneficial for the overweight child with PKU.


Adult pancreatic acinar cells dedifferentiate to an embryonic progenitor phenotype with concomitant activation of a senescence programme that is present in chronic pancreatitis.
Acinar cells display plasticity in vitro and in vivo and can activate a variety of differentiation programmes that may contribute to pancreatic diseases. The aims were to determine: (1) the differentiation potential of acinar cells under conditions which favour stem cell survival, and (2) its relationship to the phenotypes acquired by pancreatic epithelial cells in chronic pancreatitis. Murine acinar cells were cultured in suspension and their molecular phenotype was characterised by qRT-PCR, chromatin immunoprecipitation, immunocytochemistry and global transcriptome analysis. These findings were compared to the changes occurring in experimental chronic pancreatitis induced by pancreatic duct ligation and chronic caerulein administration. Acinar cells in suspension culture acquired a dedifferentiated phenotype characteristic of pancreatic embryonic progenitors, consisting of the co-expression of Ptf1a and Pdx1, presence of an embryonic-type PTF1 transcriptional complex, activation of the Notch pathway, and expression of additional pancreatic progenitor cell markers such as CpA1, Sox9 and Hnf1b. A senescence programme, associated with activation of Ras and ERK signalling, limited the proliferative capacity of the cells. A similar progenitor-like phenotype with activation of a senescence programme was observed in experimental chronic pancreatitis induced by pancreatic duct ligation or repeated caerulein administration, with the concomitant and differential activation of proliferation and senescence in distinct cell populations. Acinar cells dedifferentiate into an embryonic progenitor-like phenotype upon suspension culture. This is associated with the activation of a senescence programme. Both processes take place in experimental chronic pancreatitis where senescence may contribute to limit tumour progression.


Genetic characteristics of clones derived from measles virus strain L-16.
The L-16 vaccine strain of measles virus produced in L-41 cell cultures of various size (0.5-0.2 mm in diameter), with clear or opaque centers, thus being genetically heterogeneous by the S and P markes. The clones derived from the L-16 strain differed from it and from each other in a number of genetic properties. Clones isolated at different temperatures, 35 degrees or 32 degrees C, differed from each other in thermostability, sensitivity to interferon, interferon-inducing activity, antigenicity and plaque size. Marked correlations were established between cytopathic activity (TC) and reproductive activity in L-41 cell cultures; thermostability at 50 degrees C (T50 character) and inactivation constant; and interferon-inducing activity and sensitivity to interferon.


Substrate recognition by osteoclast precursors induces C-src/microtubule association.
The osteoclast is distinguished from other macrophage polykaryons by its polarization, a feature induced by substrate recognition. The most striking component of the polarized osteoclast is its ruffled membrane, probably reflecting insertion of intracellular vesicles into the bone apposed plasmalemma. The failure of osteoclasts in c-src-/- osteopetrotic mice to form ruffled membranes indicates pp60(c-src) (c-src) is essential to osteoclast polarization. Interestingly, c-src itself is a vesicular protein that targets the ruffled membrane. This being the case, we hypothesized that matrix recognition by osteoclasts, and their precursors, induces c-src to associate with microtubules that traffic proteins to the cell surface. We find abundant c-src associates with tubulin immunoprecipitated from avian marrow macrophages (osteoclast precursors) maintained in the adherent, but not nonadherent, state. Since the two proteins colocalize only within adherent avian osteoclast-like cells examined by double antibody immunoconfocal microscopy, c-src/tubulin association reflects an authentic intracellular event. C-src/tubulin association is evident within 90 min of cell-substrate recognition, and the event does not reflect increased expression of either protein. In vitro kinase assay demonstrates tubulin-associated c-src is enzymatically active, phosphorylating itself as well as exogenous substrate. The increase in microtubule-associated kinase activity attending adhesion mirrors tubulin-bound c-src and does not reflect enhanced specific activity. The fact that microtubule-dissociating drugs, as well as cold, prevent adherence-induced c-src/tubulin association indicates the protooncogene complexes primarily, if not exclusively, with polymerized tubulin. Association of the two proteins does not depend upon protein tyrosine phosphorylation and is substrate specific, as it is induced by vitronectin and fibronectin but not type 1 collagen. Finally, consistent with cotransport of c-src and the osteoclast vacuolar proton pump to the polarized plasmalemma, the H+-ATPase decorates microtubules in a manner similar to the protooncogene, specifically coimmunoprecipitates with c-src from the osteoclast light Golgi membrane fraction, and is present, with c-src, in preparations enriched with acidifying vesicles reconstituted from the osteoclast ruffled membrane.


Cavity QED with a Bose-Einstein condensate.
Cavity quantum electrodynamics (cavity QED) describes the coherent interaction between matter and an electromagnetic field confined within a resonator structure, and is providing a useful platform for developing concepts in quantum information processing. By using high-quality resonators, a strong coupling regime can be reached experimentally in which atoms coherently exchange a photon with a single light-field mode many times before dissipation sets in. This has led to fundamental studies with both microwave and optical resonators. To meet the challenges posed by quantum state engineering and quantum information processing, recent experiments have focused on laser cooling and trapping of atoms inside an optical cavity. However, the tremendous degree of control over atomic gases achieved with Bose-Einstein condensation has so far not been used for cavity QED. Here we achieve the strong coupling of a Bose-Einstein condensate to the quantized field of an ultrahigh-finesse optical cavity and present a measurement of its eigenenergy spectrum. This is a conceptually new regime of cavity QED, in which all atoms occupy a single mode of a matter-wave field and couple identically to the light field, sharing a single excitation. This opens possibilities ranging from quantum communication to a wealth of new phenomena that can be expected in the many-body physics of quantum gases with cavity-mediated interactions.


Quantitative assessment of the cell penetrating properties of RI-Tat-9: evidence for a cell type-specific barrier at the plasma membrane of epithelial cells.
Penetration of epithelial cells represents the rate-determining step for the absorption of many drugs and pharmaceutical macromolecules such as proteins and nucleic acid therapeutics. While the potential of using cell-penetrating peptides (CPPs) to facilitate absorption has been increasingly recognized, the mechanism of cell penetration and the uptake into certain cells have recently been called into question due to methodological artifacts. Therefore, the objective of this study was to quantitatively assess the ability of RI-Tat-9, a proteolytically stable CPP, to penetrate epithelial cell monolayers. The permeability of RI-Tat-9 with two epithelial cell lines, Madin-Darby canine kidney (MDCK) and Caco-2 cells, was comparable to the leakiness of the respective intact monolayers. Microscopic imaging showed that fluorescence-tagged RI-Tat-9 did not enter these cells, further supporting a paracellular transport mechanism. Although insufficient data were generated in these studies to generalize the observed phenomenon, the entry of RI-Tat-9 into nonepithelial T lymphocytic MT2 cells, possibly by endocytosis, suggested that a cell type-specific barrier might exist that controlled uptake of RI-Tat-9 by cells. Compared to that in MT2 and HeLa cells, the active uptake of the peptide into MDCK monolayers was much slower and showed no dependence of cell energy. Furthermore, the equilibrium binding of RI-Tat-9 to MDCK cells at 0 degrees C was indicative of an interaction with a nonspecific receptor. A correlation between binding density and concentration difference across a leaky separation barrier suggested that repulsion of free peptide molecules by bound peptide molecules at the MDCK monolayer surface may be significant at micromolar concentrations. The results of this study quantitatively show that Tat CPP uptake into two commonly used epithelial cell types is minimal and possibly cell type-specific. Implications for Tat CPP-assisted drug delivery are discussed.


The lipase-catalyzed hydrolysis of lutein diesters in non-aqueous media is favored at extremely low water activities.
The enzymatic hydrolysis of a mixture of lutein diesters from Marigold flower (Tagetes erecta) was performed both in organic solvents and supercritical CO(2) (SC-CO(2)) using two commercial lipases: lipase B from Candida antarctica (Novozym 435) and the lipase from Mucor miehei (Lipozyme RM IM). Both lipases showed an unexpected dependence of initial reaction rate with the initial water activity (a(wi)) in hexane, with the highest rates of hydrolysis taking place at the lowest a(wi) of the biocatalyst particles. The same result was observed using isooctane, toluene, or SC-CO(2). It is proposed that an increase in a(wi) generates a hydrophilic microenvironment that prevents efficient partitioning of the highly hydrophobic lutein diesters to the enzyme. The critical role of water in this system has not been reported for other hydrolytic reactions in low water media. Calculations of water available for hydrolysis from isotherm analysis, Karl-Fischer titration, and substrate conversion at a(wi) = 0.13, indicate that the extent of reaction is not limited by the amount of available water. Accordingly, the enzyme that holds the largest amount of water after prehydration at the same a(wi) (0.13) will yield the greatest substrate conversion and concentration of the free lutein product. The highest conversion occurred in SC-CO(2), which opens up new opportunities to develop a combined extraction-reaction process for the environmentally benign synthesis of lutein, an important nutraceutical compound.


Formation of DNA adducts in wild-type and transgenic mice expressing human sulfotransferases 1A1 and 1A2 after oral exposure to furfuryl alcohol.
Furfuryl alcohol (FFA) is present in many heat-treated foods as a result of its formation via dehydration of pentoses. It is also used legally as a flavouring agent. In an inhalation study conducted in the National Toxicology Program, FFA showed some evidence of carcinogenic activity in rats and mice. FFA was generally negative in conventional genotoxicity assays, which suggests that it may be a non-genotoxic carcinogen. However, it was recently found that FFA is mutagenic in Salmonella strains expressing appropriate sulfotransferases (SULTs), such as human or mouse SULT1A1. The same DNA adducts that were formed by FFA in these strains, mainly N (2)-((furan-2-yl)methyl)-2'-deoxyguanosine (N (2)-MF-dG), were also detected in tissues of FFA-exposed mice and even in human lung specimens. In the present study, a single oral dose of FFA (250 mg/kg body weight) or saline was administered to FVB/N mice and transgenic mice expressing human SULT1A1/1A2 on the FVB/N background. The transgenic mice were used, since human and mouse SULT1A1 substantially differ in substrate specificity and tissue distribution. DNA adducts were studied in liver, kidney, proximal and distal small intestine as well as colon, using isotope-dilution ultra performance liquid chromatography (UPLC-MS/MS). Surprisingly, low levels of adducts that may represent N (2)-MF-dG were detected even in tissues of untreated mice. FFA exposure enhanced the adduct levels in colon and liver, but not in the remaining investigated tissues of wild-type (wt) mice. The situation was similar in transgenic mice, except that N (2)-MF-dG levels were also strongly enhanced in the proximal small intestine. These different results between wt and transgenic mice may be attributed to the fact that human SULT1A1, but not the orthologous mouse enzyme, is strongly expressed in the small intestine.


Intracellular signal transduction pathways induced by leptin in C2C12 cells.
As experimental evidence suggests that leptin may have direct effects on peripheral tissues, we investigated some of the transductional molecules induced by leptin in C2C12 cells. In immunoprecipitation experiments using anti-p85 antibodies (a regulatory subunit of phosphatidylinositol-3-kinase; PI3K), we observed a significant increase in PI3K activity. Immunoblot analyses showed that Akt, GSK3, ERK1, ERK2, and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation significantly increased after leptin treatment. Protein kinase C (PKC)-zeta was also activated by leptin, as documented by an immunocomplex kinase assay and immunoblotting experiments. The treatment of C2C12 cells with Wortmannin before leptin administration inhibited induction of the phosphorylation of ERKs (extracellular signal-regulated kinases) but not that of p38 MAPK, whereas pre-treatment with a PKC-zeta inhibitor partially decreased ERK phosphorylation. Taken together, our in vitro results further support the hypothesis that leptin acts acutely on skeletal muscle tissue through some of the components of insulin signalling, including PKC-zeta.


Tensile strength of ligaments after thermal shrinkage depending on time and immobilization: in vivo study in the rabbit.
The effects of immobilization on healing collagenous tissue treated with thermal shrinkage are investigated in an in vivo rabbit model. Thermal shrinkage was performed on 45 of 50 medial collateral ligaments in 25 mature New Zealand rabbit knees. In half of the knees, the joints were immobilized. Animals were killed at 0, 3, 6, and 9 weeks postoperatively. Failure loads of ligaments were determined, and morphologic changes were evaluated by electron microscopy. The failure load of shrunken ligaments was significantly lower than that of the intact ligaments on the day of operation (P<.05). Shrunken ligaments reached their highest failure loads in the third week within the first 9 weeks. The immobilized ligaments remained weaker than the mobile group, but this difference was statistically significant only in the ninth week (P<.05). Immobilization seems to have negative effects on the healing ligament. Ideal timing for remobilization is still controversial, and abandoning immobilization protocols for longer than 3 weeks should be considered.


Multiple Recombination Events Drive the Current Genetic Structure of Xanthomonas perforans in Florida.
Prior to the identification of Xanthomonas perforans associated with bacterial spot of tomato in 1991, X. euvesicatoria was the only known species in Florida. Currently, X. perforans is the Xanthomonas sp. associated with tomato in Florida. Changes in pathogenic race and sequence alleles over time signify shifts in the dominant X. perforans genotype in Florida. We previously reported recombination of X. perforans strains with closely related Xanthomonas species as a potential driving factor for X. perforans evolution. However, the extent of recombination across the X. perforans genomes was unknown. We used a core genome multilocus sequence analysis approach to identify conserved genes and evaluated recombination-associated evolution of these genes in X. perforans. A total of 1,356 genes were determined to be "core" genes conserved among the 58 X. perforans genomes used in the study. Our approach identified three genetic groups of X. perforans in Florida based on the principal component analysis (PCA) using core genes. Nucleotide variation in 241 genes defined these groups, that are referred as Phylogenetic-group Defining (PgD) genes. Furthermore, alleles of many of these PgD genes showed 100% sequence identity with X. euvesicatoria, suggesting that variation likely has been introduced by recombination at multiple locations throughout the bacterial chromosome. Site-specific recombinase genes along with plasmid mobilization and phage associated genes were observed at different frequencies in the three phylogenetic groups and were associated with clusters of recombinant genes. Our analysis of core genes revealed the extent, source, and mechanisms of recombination events that shaped the current population and genomic structure of X. perforans in Florida.


Roseomonas bella sp. nov., isolated from lake sediment.
A Gram-stain-negative, non-motile, coccus-shaped, catalase- and oxidase-positive, facultatively anaerobic and pink-pigmented bacterium, designated strain CQN31T, was isolated from sediment of Changqiaohai Lake, Yunnan Province, China. Growth occurred at 4-45 °C (optimum, 37 °C), at pH 6.5-9.5 (optimum, pH 8.0) and with 0-1 % (w/v) NaCl (optimum, 0 %). C18 : 1 ω7c/C18 : 1 ω6c and C16 : 0 were the predominant fatty acids. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), phosphatidyldimethylethanolamine (PME) and one unidentified aminolipid (AL) were the major polar lipids. The G+C content of the genomic DNA was 71.5 %. 16S rRNA gene sequence comparisons indicated that strain CQN31T shared 96.8 % similarity with Roseomonas wooponensis JCM 19527T and 95.9 % with R. terricola EM0302T. Digital DNA-DNA hybridization values between strain CQN31T and Roseomonas stagni DSM 19981T, R. rosea DSM 14916T and R. mucosa NCTC 13291T were 21.0, 19.4 and 19.8 %, respectively. Average amino acid identity and average nucleotide identity values between strain CQN31T and R. stagni DSM 19981T, R. rosea DSM 14916T and R. mucosa NCTC 13291T were 73.7, 63.4 and 61.9 %, and 79.2, 77.1 and 77.5%, respectively. Distinct morphological, physiological and genotypic differences from previously described taxa support the classification of strain CQN31T as a representative of a novel species in the genus Roseomonas, for which the name Roseomonas bella sp. nov. is proposed. The type strain is CQN31T (=KCTC 62447T=MCCC 1H00309T).


[Problems of plastic and reconstructive surgery in the face].
For reconstruction of extensive skin defects on the face two techniques can be suggested: the sliding graft from the area of the skin adjacent to the defect (technique of the sliding graft and rotation) and the technique of distant flaps. If possible preference should be given to the first technique, as it certainly leads to better results regarding function, form and structure of the skin.


Ultrastructure of the epithelial cells associated with tooth biomineralization in the chiton Acanthopleura hirtosa.
The cusp epithelium is a specialized branch of the superior epithelium that surrounds the developing teeth of chitons and is responsible for delivering the elements required for the formation of biominerals within the major lateral teeth. These biominerals are deposited within specific regions of the tooth in sequence, making it possible to conduct a row by row examination of cell development in the cusp epithelium as the teeth progress from the unmineralized to the mineralized state. Cusp epithelium from the chiton Acanthopleura hirtosa was prepared using conventional chemical and microwave assisted tissue processing, for observation by light microscopy, conventional transmission electron microscopy (TEM) and energy filtered TEM. The onset of iron mineralization within the teeth, initiated at row 13, is associated with a number of dramatic changes in the ultrastructure of the apical cusp cell epithelium. Specifically, the presence of ferritin containing siderosomes, the position and number of mitochondria, and the structure of the cell microvilli are each linked to aspects of the mineralization process. These changes in tissue development are discussed in context with their influence over the physiological conditions within both the cells and extracellular compartment of the tooth at the onset of iron mineralization.


Differentiation of cerebellar cell identities in absence of Fgf signalling in zebrafish Otx morphants.
Although the secreted molecule Fgf8 is a key player of the isthmic organiser function, the mechanisms by which it acts remain unclear. Here, we present evidence indicating that Fgf8 is not instructive in establishing zebrafish cerebellar cell identities, although it is required for proliferation and morphogenesis of this territory. We first show that, as in mouse, lack of Otx function in zebrafish leads to transformation of the presumptive mesencephalon into an extended rhombomere 1 (r1). Expanded Fgf8 expression was proposed to be the cause of this fate transformation. However, this report demonstrates that zebrafish embryos lacking both Otx and fgf8 functions retain an extended r1 and display differentiation of at least two cerebellar cell fates. We show that this is not caused by presence of other Fgfs, which implies that in absence of Otx, Fgf function is not necessary for the differentiation of cerebellar cell types. Otx proteins are therefore potent repressors of cerebellar fates, kept out of r1 progeny by Fgf8. Because Otx transcripts are not present in presumptive r1 territory prior to fgf8 expression, Fgf8 is required to maintain, rather than induce, the posterior boundary of Otx expression. This maintenance is enough to allow cerebellar differentiation.


Towards a definition of the term and concept of interaction.
Although often used descriptively, the concept 'interaction' has not been an inherently psychoanalytic term. It suggests an external or social purview, rather than an intrapsychic one. If, however, the term were qualified to convey 'experienced' interaction and a clear delineation were maintained between the point-of-view of the patient and that of the analyst or other outside observer, 'interaction' might then be credibly employed within the psychoanalytic lexicon. For in this way the investigative terrain remains the patient's psychical reality--with its conscious and unconscious, conflictual, defensive and imaginative expressions still our fundamental purview. Clinical examples are offered to illustrate a sharpened focus on interaction as seen from the patient's point-of-view to highlight the implications of this position in furthering our psychoanalytic inquiry.


Silibinin induced apoptosis of human epidermal cancer A431 cells by promoting mitochondrial NOS.
The antitumor effects of silibinin are of increasing interest, though its mechanism is not yet clear. The goal of this study was to clarify the mechanism of silibinin-induced cell death in the A431 human epidermoid carcinoma cell line. We used a cell viability assay, flow cytometry, nitric oxide (NO) assay, and western blotting to examine relationships between silibinin, NO generation and apoptosis in A431 cells. Silibinin inhibited A431 cell growth in a dose-dependent manner, inducing mitochondrial damage, and apoptosis at a high dose. At the same time, high dose silibinin increased NO levels in A431 cells and the endothelial nitric oxide synthase (eNOS) inhibitor NG-nitro-L-arginine methylester (L-NAME) attenuated silibinin-induced cell growth inhibition. By western blotting, silibinin caused increased eNOS phosphorylation in the mitochondria. The AMP-activated protein kinase inhibitor compound C significantly decreased p-eNOS expression, while blocking eNOS did not affect p-AMPK levels, suggested that AMPK acted upstream of eNOS. This study showed that silibinin increased NO levels in A431 cells by activating the AMPK-eNOS pathway, leading to mitochondrial dysfunction and apoptosis. In this mechanism of action, mitochondrial eNOS played an important role. The results provided new understanding of the functions of intracellular NO.


Coinfection modulates inflammatory responses, clinical outcome and pathogen load of H1N1 swine influenza virus and Haemophilus parasuis infections in pigs.
Respiratory co-infections are important factor affecting the profitability of pigs production. Swine influenza virus (SIV) may predispose to secondary infection. Haemophilus parasuis (Hps) can be a primary pathogen or be associated with other pathogens such as SIV. To date, little is known about the effect of coinfection with SIV and Hps on the disease severity and inflammatory response and the role of Hps in the induction of pneumonia in the absence of other respiratory pathogens. In the study we investigated the influence of SIV and Hps coinfection on clinical course, inflammatory response, pathogens shedding and load at various time points following intranasal inoculation. The correlation between local concentration of cytokines and severity of disease as well as serum acute phase proteins (APP) concentration has been also studied. All co-infected pigs had fever, while in single inoculated pigs fever was observed only in part of animals. Necropsy revealed lesions in the lungs all SIV-inoculated and co-inoculated pigs, while in Hps-single inoculated animals only 1 out of 11 pigs revealed gross lung lesions. The SIV shedding was the highest in co-inoculated pigs. There were no differences between Hps-single inoculated and co-inoculated groups with regard to Hps shedding. The significant increase in Hps titre in the lung has been found only in co-inoculated group. All APP increased after co-infection. In single-inoculated animals various kinetics of APP response has been observed. The lung concentrations of cytokines were induced mostly in SIV + Hps pigs in the apical and middle lobe. These results correlated well with localization of gross lung lesions. The results revealed that SIV increased the severity of lung lesions and facilitated Hps (PIWetHps192/2015) replication in the porcine lung. Furthermore, Hps influenced the SIV nasal shedding. Enhanced Hps and SIV replication, together with stronger systemic and local inflammatory response contributed to a more severe clinical signs and stronger, earlier immune response in co-inoculated animals. We confirmed the previous evidence that single-Hps infection does not produce significant pneumonic lesions but it should be in mind that other strains of Hps may produce lesions different from that reported in the present study.


Oxidative Stress and Inflammation, MicroRNA, and Hemoglobin Variations after Administration of Oxygen at Different Pressures and Concentrations: A Randomized Trial.
Exercise generates reactive oxygen species (ROS), creating a redox imbalance towards oxidation when inadequately intense. Normobaric and hyperbaric oxygen (HBO) breathed while not exercising induces antioxidant enzymes expression, but literature is still poor. Twenty-two athletes were assigned to five groups: controls; 30%, or 50% O2; 100% O2 (HBO) at 1.5 or 2.5 atmosphere absolute (ATA). Twenty treatments were administered on non-training days. Biological samples were collected at T0 (baseline), T1 (end of treatments), and T2 (1 month after) to assess ROS, antioxidant capacity (TAC), lipid peroxidation, redox (amino-thiols) and inflammatory (IL-6, 10, TNF-α) status, renal function (i.e., neopterin), miRNA, and hemoglobin. At T1, O2 mixtures and HBO induced an increase of ROS, lipid peroxidation and decreased TAC, counterbalanced at T2. Furthermore, 50% O2 and HBO treatments determined a reduced state in T2. Neopterin concentration increased at T1 breathing 50% O2 and HBO at 2.5 ATA. The results suggest that 50% O2 treatment determined a reduced state in T2; HBO at 1.5 and 2.5 ATA similarly induced protective mechanisms against ROS, despite the latter could expose the body to higher ROS levels and neopterin concentrations. HBO resulted in increased Hb levels and contributed to immunomodulation by regulating interleukin and miRNA expression.


Cardiac autonomic involvement and peripheral nerve function in patients with diabetic neuropathy.
The aim of our study was to investigate the relationship between cardiac autonomic neuropathy and dysfunction of myelinated and unmyelinated nerve fibres in the peripheral nerve. We measured nerve conduction velocities, warmth/cold perception thresholds at the foot dorsum, sympathetic skin response (SSR), and performed the quantitative sudomotor axon reflex test (QSART). Forty-three diabetic patients with distal-symmetric polyneuropathy were included. According to the results of heart rate variation, 20 patients had cardiac autonomic neuropathy (CAN+). Apart from motor nerve conduction velocities, all tests were more often abnormal in CAN+ patients. Warmth thresholds (afferent C-fibres) and reduced compound muscle action potentials (CMAPs) of the tibial and peroneal nerve, indicating axonal damage, were more often abnormal in CAN+. Cold threshold and sural nerve conduction velocity were indicators of involvement of myelinated small and large nerve fibres, but not of the cardiac autonomic system. Ninety-four percent (94%) of patients with absent SSR and 78% of patients with abnormal QSART had CAN+. SSR and QSART may be useful for assessment of autonomic neuropathy in diabetic patients with cardiac arrhythmia where direct measurement of heart rate variability is not possible. In the majority of our patients with CAN+, the vagal-cardiac and the sudomotor-sympathetic systems were involved simultaneously, although two entirely different systems were tested. This may reflect a C-fibre directed selectivity of the pathological process in autonomic diabetic neuropathy. In conclusion our results show that diabetics with and without cardiac autonomic neuropathy have a different profile of involvement of peripheral nerve fibres.


An exploratory non-randomized study of a 3-month electronic nicotine delivery system (ENDS) intervention with people accessing a homeless supported temporary accommodation service (STA) in Ireland.
Smoking is endemic amongst people accessing homeless services, and they are disproportionately affected by smoking-related diseases. This paper reports on the results of a 3-month small scale intervention which explored the efficacy, challenges and opportunities of using electronic nicotine delivery systems (ENDS) to support cessation of tobacco smoking with people accessing an Irish supported temporary accommodation (STA) homeless service. It considers the results of this intervention with reference to the balance of harms between the use of vaping to support smoking cessation and continued smoking. Twenty-three participants were recruited. Demographic data, carbon monoxide (CO) measurements, homelessness status and smoking history were recorded. Participants were given an ENDS device and two 10-ml bottles containing e-liquid available in several flavours and at several strengths. Participants could pick up new bottles on a weekly basis. At weeks 1, 4, 8 and 12, the Fagerström Test and Mood and Physical Symptoms Scale (MPSS) were administered. Over 75% of the residents in the participating hostel were recruited (23/30). However, there was a substantial loss to follow-up (n = 14) as a result of data protection issues, the transient nature of the population of interest and non-compliance with the intervention. Self-reported reductions in cigarette consumption were found to be statistically significant (p < 0.001). However, reductions in carbon monoxide measurements were not statistically significant. Decreases in Fagerström Nicotine Dependence Test were statistically significant (p = 0.001), but decreases in MPSS "urge to smoke" and "strength of urges" composite scores were not. Reported side effects included coughing, runny nose, bleeding nose, slight sweating, dizziness, increased phlegm and a burning sensation at the back of the throat. Barriers to engagement were peer norms, vaping restrictions in accommodation and adverse life events. Positive effects reported included increased energy, less coughing, better breathing and financial benefits. An improvement in the domain "poor concentration" was also found to be statistically significant (p = 0.040). ENDS-based interventions may be effective with this population. Future research should aim to improve follow-up, consider including behavioural components and monitor health effects in relation to ongoing concerns around risks and the balance of harms. Registered retrospectively ISRCTN14767579.


Thought Disorder on Object Sorting Test Is Associated with Executive Dysfunction in Schizophrenia.
Thought disorder is considered to be central to the core disturbances in schizophrenia and was described by Goldstein as aberrant "concept formation." Executive dysfunction is another core deficit in schizophrenia. With a greater emphasis on psychopathology in nosological systems, the classical thought disorder receives less prominence. The present study aimed to understand the association between classical thought disorder (aberrant concept formation and concrete abstraction) and executive dysfunction. Thirty patients with schizophrenia and thirty healthy subjects, matched on age, gender, education, and socioeconomic status, were screened using MINI 5.0, following which they were assessed on object sorting test (OST) and selected tests for executive functions (EFs). Individuals with schizophrenia were found to have significantly decreased performance on all domains of EFs and OST. Total peculiar scores on OST were significantly associated with mental speed, focused attention, and divided attention. Total impoverished scores on OST was significantly associated with focused attention, sustained attention, planning, set shifting, perseveration, and concept formation. Several correlations, among performance on OST and neuropsychological tests, suggest that patterns of responses on OST can point to underlying executive dysfunction. Both thought disorder and executive dysfunction mirror similar constructs. This similarity represents a conceptual bridge between the classical and contemporary descriptions of the core deficits in schizophrenia.


A randomised controlled trial testing the rebound-preventing benefit of four days of prednisolone during the induction of oclacitinib therapy in dogs with atopic dermatitis.
A rebound of pruritus occasionally occurs after oclacitinib dose reduction in dogs with atopic dermatitis (AD). To determine whether an initial 4-day course of prednisolone decreases the probability of a pruritus rebound after reducing the frequency of oclacitinib administration. Forty dogs with mild-to-moderate AD lesions and moderate-to-severe pruritus. Dogs were randomised to receive oclacitinib at 0.4-0.6 mg/kg twice daily for 14 days then once daily, alone or with prednisolone at 0.5 mg/kg, orally, twice daily for the first 4 days. Clinicians graded the Canine Atopic Dermatitis Extent and Severity Index (CADESI)4 and 2D-investigator global assessment (IGA) before and after 28 days; owners assessed the pruritis Visual Analog Scale (PVAS)10 and Owner Global Assessment of Treatment Efficacy (OGATE) on Day (D)0, D4, D14, D21 and D28. We considered a rebound any increase greater than one PVAS10 grade at D21 compared to D14. On D21, there were significantly fewer rebounds in the dogs receiving prednisolone (three of 20, 15%) compared to those given oclacitinib alone (nine of 20, 45%; Fisher's test, p = 0.041). Compared to oclacitinib monotherapy, the concurrent administration of prednisolone for the first 4 days led to significantly lower PVAS10 on D4 and D28, CADESI4 and 2D-IGA on D28, and OGATE on D21 and D28 (Wilcoxon-Mann-Whitney U-tests). Adverse effects of therapy were minor, intermittent and self-resolving. The initial addition of 4 days of prednisolone significantly decreased the probability of a rebound of pruritus 1 week after oclacitinib dose reduction. This short concomitant glucocorticoid administration led to a higher skin lesion improvement and improved perception of treatment efficacy with minimal adverse effects.


Towards evidence-based, quality-controlled health promotion: the Dutch recognition system for health promotion interventions.
Registration or recognition systems for best-practice health promotion interventions may contribute to better quality assurance and control in health promotion practice. In the Netherlands, such a system has been developed and is being implemented aiming to provide policy makers and professionals with more information on the quality and effectiveness of available health promotion interventions and to promote use of good-practice and evidence-based interventions by health promotion organizations. The quality assessments are supervised by the Netherlands Organization for Public Health and the Environment and the Netherlands Youth Institute and conducted by two committees, one for interventions aimed at youth and one for adults. These committees consist of experts in the fields of research, policy and practice. Four levels of recognition are distinguished inspired by the UK Medical Research Council's evaluation framework for complex interventions to improve health: (i) theoretically sound, (ii) probable effectiveness, (iii) established effectiveness, and (iv) established cost effectiveness. Specific criteria have been set for each level of recognition, except for Level 4 which will be included from 2011. This point of view article describes and discusses the rationale, organization and criteria of this Dutch recognition system and the first experiences with the system.


The characteristics of compassionate care during childbirth according to midwives: a qualitative descriptive inquiry.
Although compassion is considered to be of prime importance in nursing and midwifery, there is no clear understanding of what compassionate care in childbirth entails, and how midwives perceive compassionate care is largely unknown. This study accordingly seeks to describe the characteristics, of compassionate care during childbirth as perceived by midwives. A qualitative descriptive inquiry was undertaken with a voluntary online survey, where participants were recruited via snowball sampling on the social networking site, Facebook. The participants were midwives, and the unit of analysis was the received responses. Participants reported on instances of compassionate care during childbirth. The data was thematically analysed using Tesch's eight steps to identify common themes. Ninety-eight responses were analysed and three themes with eight sub-themes emerged as dominant characteristics. Themes and sub-themes were as follows: making meaningful connections with women (displaying good interpersonal skills, conduct based on dignity and respect, establishing trust); initiating individualised understanding of each woman (showing empathy, permitting maternal choice) and action through care and support (providing emotional support, assistance through instrumental care, continuous informational support). In seeking to determine what characterises compassionate care in childbirth, the findings reveal a process of making meaningful connections with women through recognising their needs, initiating individualised understanding of each woman's needs and desiring to ease it, which is subsequently manifested in action through emotional, instrumental and informational care and support. A better understanding of how midwives perceive compassionate care could potentially improve the quality of care midwives offer during childbirth.


"Know That You're Not Just Settling": Exploring Women Athletes' Self-Compassion, Sport Performance Perceptions, and Well-Being Around Important Competitive Events.
Self-compassion, an adaptive self-attitude, is a resource that women athletes use during emotionally difficult times and as a way to reach their potential. The relationship between self-compassion and sport performance, however, is complex. The role and experience of self-compassion within perceived important competitive events are important to explore, as athletes face unique pressures and stressors in these meaningful sport experiences. This collective case study describes women athletes' self-compassion, sport performance perceptions, and well-being around a self-identified important competitive event. Competitive women athletes (N = 9) participated in two one-on-one interviews, before and after their important competitive event. Results from the holistic, functional, and thematic analyses are represented by holistic case descriptions and an overarching theme, Continuing to Excel in Sport, and subthemes, Reframing Criticism and A Determined Approach. In important competitive events, women athletes utilize self-compassion to promote performance perceptions and well-being when preparing, competing, and reflecting to excel in sport.


Characteristics of evoked potentials and single neuron responses in the cat sensorimotor cortex to sound stimuli with different frequencies.
The characteristics of the averaged evoked potentials (AEP) (experiments with awake non-paralysed animals), of the evoked potentials (EP) and of the responses of single sensorimotor cortical neurons (acute experiments) of cats to tone-bursts with frequencies within 0.1-6.0 kHz were studied. Response selectivity to the tone-burst frequencies which are energetically pronounced in some biologically significant sounds for the cat was observed. The averaged curve of the dependence of the amplitude of AEP in the somatosensory cortical region (S1) on the tone-burst frequency has reliable maximum values at the frequencies of 0.8, 1.6 and 2.0-3.0 kHz. Most pronounced changes in the heart rhythm were observed within the tone-burst frequency ranges in which the AEP of the highest amplitudes were recorded. The amplitude of the AEP was found to increase during the conditioned reflex elaboration. The curve of the dependence of the probability of the EP occurrence on the frequency at equal sound pressure levels had maximum values at the frequencies of 1.6 and 3.2 kHz. The highest amplitude values of EP were found at frequencies of 0.8, 1.6 and 3.2 kHz. More than half of the recorded neurons revealed the lowest values of the response thresholds and the maximum values of the occurrence probability under suprathreshold stimulation at frequencies close to 0.8, 1.6, and 3.2 kHz. It is supposed that the above mentioned feature of the input frequency organization in sensorimotor cortex is connected with the selectivity as to the biological significance of acoustic stimuli.


Unperturbed posttranscriptional regulatory Rev protein function and HIV-1 replication in astrocytes.
Astrocytes protect neurons, but also evoke proinflammatory responses to injury and viral infections, including HIV. There is a prevailing notion that HIV-1 Rev protein function in astrocytes is perturbed, leading to restricted viral replication. In earlier studies, our finding of restricted viral entry into astrocytes led us to investigate whether there are any intracellular restrictions, including crippled Rev function, in astrocytes. Despite barely detectable levels of DDX3 (Rev-supporting RNA helicase) and TRBP (anti-PKR) in primary astrocytes compared to astrocytic cells, Rev function was unperturbed in wild-type, but not DDX3-ablated astrocytes. As in permissive cells, after HIV-1 entry bypass in astrocytes, viral-encoded Tat and Rev proteins had robust regulatory activities, leading to efficient viral replication. Productive HIV-1 infection in astrocytes persisted for several weeks. Our findings on HIV-1 entry bypass in astrocytes demonstrated that the intracellular environment is conducive to viral replication and that Tat and Rev functions are unperturbed.


An Extension of the i2b2 Data Warehouse to Support REDCap Dynamic Data Pull.
i2b2 and REDCap are two widely adopted solutions respectively to facilitate data re-use for research purpose and to manage non-for-profit research studies. REDCap provides the design specifications to build a web service used to import data from an external source with a procedure called DDP. In this work we have developed a web service that implements these specifications in order to import data from i2b2. Our approach has been tested with a real REDCap study.


Scuticociliate (Philasterides dicentrarchi) infection cluster in a multispecies marine aquarium system.
Scuticociliatosis, caused by ciliated protozoa of the subclass Scuticociliatia, has been associated with high mortalities in marine fish. Environmental factors such as an increase in water temperature can enhance this disease. The aim of the present report is to describe the occurrence of a cluster of cases of scuticociliatosis in a multispecies marine cold-water system in a public aquarium. Philasterides dicentrarchi was identified by PCR in formalin-fixed tissues of some of the fish showing meningitis or meningoencephalitis, dermatitis and myositis with intralesional protozoa. An increase in water temperature of approximately 2°C was identified as a potential contributing factor for this cluster of infections. Higher temperature may have enhanced the propagation or pathogenicity of scuticociliates or increased host susceptibility of some species of fish, especially wolf-eel Anarrhichthys ocellatus and spotted ratfish Hydrolagus colliei. This report also highlights the complexity of dealing with mixed species systems housing fish from different natural ecozones.


Insulin Autoimmune Syndrome: A Case of Clopidogrel-induced Autoimmune Hypoglycemia.
Insulin autoimmune syndrome (IAS) is characterized by hyperinsulinemic hypoglycemia with elevated anti-insulin antibodies. Most commonly observed in the Japanese population, elsewhere it is rare and associated with autoimmune diseases, plasma cell dyscrasias, or sulfhydryl group medications. The active metabolite of clopidogrel has a sulfhydryl group and here we report a case of clopidogrel-induced IAS. A 67-year-old man was admitted with severe hyperinsulinemic hypoglycemia requiring continuous intravenous infusion of 10% dextrose to sustain euglycemia. His symptoms of hypoglycemia had started after commencing dual antiplatelet therapy (including clopidogrel) for ischemic heart disease 9 months earlier. The hypoglycemia was associated with elevated insulin, proinsulin, c-peptide, and anti-insulin antibody titers as well as the HLA-DRB1*04 haplotype. Multiple localizing studies were negative for an insulinoma. A diagnosis of IAS was thus made. Clopidogrel cessation, oral dexamethasone, and diazoxide therapy were not sufficient to safely wean the dextrose infusion. Plasma exchange was ultimately effective. This case highlights a case of severe IAS. Given the ubiquity of clopidogrel, IAS should be remembered as a rare adverse effect.


An iron-based cytosolic catalase and superoxide dismutase mimic complex.
The development of metallodrugs with antioxidant activities is of importance as a way to protect organisms exposed to stressful conditions. Although iron chemistry in the presence of H(2)O(2) is usually associated with pro-oxidant activity, mainly via the Fenton reaction, we found that the mononuclear compound [Fe(HPClNOL)Cl(2)]NO(3) (1; C(15)H(18)Cl(3)FeN(4)O(4), a = 8.7751(3) A, b = 9.0778(4) A, c = 24.3869(10) A, beta = 93.370(2) degrees , monoclinic, P2(1)/c, Z = 4), containing the tripodal ligand 1-[bis(pyridin-2-ylmethyl)amino]-3-chloropropan-2-ol, decomposes hydrogen peroxide and superoxide anion in vitro as well as shows in vivo protection because it prevents the harmful effects promoted by H(2)O(2) on Saccharomyces cerevisiae cells, decreasing the level of lipid peroxidation. This protective effect was observed for wild-type cells, as well as for mutant cells, which do not present the antioxidant metalloenzymes catalase (Ctt1) or copper/zinc superoxide dismutase (Sod1).


Quantitative risk assessment of Listeria monocytogenes in ready-to-eat foods: the FAO/WHO approach.
Quantitative microbiological risk assessment is a very new and unique scientific approach able to link, for the first time, data from food (in the farm-to-fork continuum) and the various data on human disease to provide a clear estimation of the impact of contaminated food on human public health. The Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) have recently launched risk assessment studies of a number of pathogen-food commodity combinations (Salmonella in eggs and in broiler chickens, Listeria monocytogenes in ready-to-eat foods, Campylobacter in broiler chickens, Vibrio in seafood) to be used to lower the risk associated with these food-borne diseases and ensure fair practices in the international trade of food. The FAO/WHO Listeria risk assessment was undertaken in part to determine how previously developed risk assessments done at the national level could be adapted or expanded to address concerns related to L. monocytogenes in ready-to-eat foods at an international level. In addition, after initiation of the risk assessment, the risk assessors were asked by the Codex Committee on Food to consider three specific questions related to ready-to-eat foods in general, which are: (1). estimate the risk for consumers in different susceptible populations groups (elderly, infants, pregnant women and immunocompromised patients) relative to the general population; (2). estimate the risk for L. monocytogenes in foods that support growth and foods that do not support growth under specific storage and shelf-life conditions; (3). estimate the risk from L. monocytogenes in food when the number of organisms ranges from absence in 25 g to 1000 colonies forming units per gram or milliliter, or does not exceed specified levels at the point of consumption. To achieve these goals, new dose-response relationships and exposure assessments for ready-to-eat foods were developed. Preliminary data indicate that eliminating the higher dose levels at the time of consumption has a large impact on the number of predicted cases.


DNA methylation-mediated down-regulation of DNA methyltransferase-1 (DNMT1) is coincident with, but not essential for, global hypomethylation in human placenta.
The genome of extraembryonic tissue, such as the placenta, is hypomethylated relative to that in somatic tissues. However, the origin and role of this hypomethylation remains unclear. The DNA methyltransferases DNMT1, -3A, and -3B are the primary mediators of the establishment and maintenance of DNA methylation in mammals. In this study, we investigated promoter methylation-mediated epigenetic down-regulation of DNMT genes as a potential regulator of global methylation levels in placental tissue. Although DNMT3A and -3B promoters lack methylation in all somatic and extraembryonic tissues tested, we found specific hypermethylation of the maintenance DNA methyltransferase (DNMT1) gene and found hypomethylation of the DNMT3L gene in full term and first trimester placental tissues. Bisulfite DNA sequencing revealed monoallelic methylation of DNMT1, with no evidence of imprinting (parent of origin effect). In vitro reporter experiments confirmed that DNMT1 promoter methylation attenuates transcriptional activity in trophoblast cells. However, global hypomethylation in the absence of DNMT1 down-regulation is apparent in non-primate placentas and in vitro derived human cytotrophoblast stem cells, suggesting that DNMT1 down-regulation is not an absolute requirement for genomic hypomethylation in all instances. These data represent the first demonstration of methylation-mediated regulation of the DNMT1 gene in any system and demonstrate that the unique epigenome of the human placenta includes down-regulation of DNMT1 with concomitant hypomethylation of the DNMT3L gene. This strongly implicates epigenetic regulation of the DNMT gene family in the establishment of the unique epigenetic profile of extraembryonic tissue in humans.


Protein losing enteropathy secondary to a pulmonary artery stent.
A 2-year-old patient with hypoplastic left heart syndrome presented 6 months following Fontan completion with protein-losing enteropathy (PLE). He had undergone stent implantation in the left pulmonary artery after the Norwood procedure, followed by redilation of the stent prior to Fontan completion. Combined bronchoscopic and catheterization studies during spontaneous breathing confirmed left bronchial stenosis behind the stent, and diastolic systemic ventricular pressure during expiration of 25 mm Hg. We postulate that the stent acts as a valve, against which the patient generates high expiratory pressures, which are reflected in the ventricular diastolic pressure. This may be the cause of PLE.


Interaction between lifestyle and genetic susceptibility in myopia: the Generation R study.
Myopia is a refractive error of the eye caused by a complex interplay between nature and nurture. The aim of this study was to investigate whether environmental risk factors can influence the genetic effect in children developing myopia. A total of 3422 children participating in the birth-cohort study Generation R underwent an extensive eye examination at 9 years with measurements of refractive error and axial length corneal radius ratio (AL/CR). Environmental risk factors were evaluated using a questionnaire, and environmental risk scores (ERS) were calculated using backward regression analyses. Genetic risk scores (GRS) were calculated based on all currently known risk variants for myopia. Gene-environment interaction (G×E) was investigated using linear and logistic regression analyses. The predictive value of G×E and parental myopia was estimated using receiver operating characteristic curves. Myopia prevalence was 12%. Both GRS (P < 0.01) and ERS (P < 0.01) were significantly associated with myopia and AL/CR, as was G×E interaction (P < 0.01 for myopia; P = 0.07 for AL/CR). The predictive value of parental myopia was 0.67 (95% CI 0.65-0.70), similar to the values of GRS (0.67; 95% CI 0.64-0.70; P = 0.98) and ERS (0.69; 95% CI 0.66-0.72; P = 0.98). Adding G×E interaction significantly improved the predictive value to 0.73 (95% CI 0.70-0.75; P < 0.01). This study provides evidence that nature and nurture are equally important for myopia and AL/CR; however, the combination has the strongest influence. Since myopia genes are common in the population, adjustment of lifestyle should be a major focus in the prevention of myopia.


[Human semen lactate dehydrogenase isoenzymes in fertility studies (author's transl)].
The lactate dehydrogenase isoenzyme pattern has been obtained in the semen of 87 males undergoing fertility studies. The proportion of LDH-X, the isoenzyme specific to the spermatozoa, is reduced in proportion to the reduction of the sperm density and motility. LDH-X is the most abundant isoenzyme in the semen of normospermic subjects. As to the other isoenzymes, the most abundant ones are the LDH-2 and the LDH-3. The results obtained lead us to conclude that the measurement of the lactate dehydrogenase isoenzymes may be useful in studies of fertility as an indicative parameter of the quality of the semen.


Mammary tumors and mammary tumor virus expression in hybrid mice of strains C57BL and GR.
Mammary tumorigenesis in genetic crosses between the high mammary tumor incidence GR and the low incidence C57BL mouse strains is highly correlated with murine mammary tumor virus expression in milk. Although the F1 and first backcross females had a mammary tumor incidence which was consistent with a single dominant gene segregation, the tumor incidence in the critical second backcross segregants disproved the single gene hypothesis. Genetic factors were clearly involved in regulation of virus expression which in turn correlated with both tumor incidence and tumor latency; these complex phenotypes are however best explained as threshold or quasicontinuous characters. As predicted from this model, the age specific incidence of mammary tumors showed a broad peak at 14-19 mo of age with no evidence of an early or late phase. Hematopoietic tumors showed no correlation with virus expression or mammary tumorigenesis suggesting different etiologies for these tumors.


Fate and impact of wastewater-borne micropollutants in lettuce and the root-associated bacteria.
The reuse of water for agricultural practices becomes progressively more important due to increasing demands for a transition to a circular economy. Treated wastewater can be an alternative option of blue water used for the irrigation of crops but its risks need to be evaluated. This study assesses the uptake and metabolization of pharmaceuticals and personal care products (PPCPs) derived from treated wastewater into lettuce as well as the impact on root-associated bacteria under a realistic and worst-case scenario. Lettuce was grown in a controlled greenhouse and irrigated with water or treated wastewater spiked with and without a mixture of fourteen different PPCPs at 10 μg/L or 100 μg/L. After harvesting the plants, the same soil was reused for a consecutive cultivation campaign to test for the accumulation of PPCPs. Twelve out of fourteen spiked PPCPs were detected in lettuce roots, and thirteen in leaves. In roots, highest concentrations were measured for sucralose, sulfamethoxazole and citalopram, while sucralose, acesulfame and carbamazepine were the highest in leaves. Higher PPCP concentrations were found in lettuce roots irrigated with spiked treated wastewater than in those irrigated with spiked water. The absolute bacterial abundance remained stable over both cultivation campaigns and was not affected by any of the treatments (type of irrigation water (water vs. wastewater) nor concentration of PPCPs). However, the irrigation of lettuce with treated wastewater had a significant effect on the microbial α-diversity indices at the end of the second cultivation campaign, and modified the structure and community composition of root-associated bacteria at the end of both campaigns. Five and fourteen bacterial families were shown to be responsible for the observed changes at the end of the first and second cultivation campaign, respectively. Relative abundance of Haliangium and the clade Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium was significantly affected in response to PCPPs exposure. Caulobacter, Cellvibrio, Hydrogenophaga and Rhizobacter were significantly affected in microcosms irrigated with wastewater.


Retrospective analysis of hops toxicosis in dogs (2002-2014): 71 cases.
To describe a population of dogs with hops toxicosis, including clinical signs observed, treatments performed, patient outcome, and overall prognosis. Clinical findings and treatment interventions were evaluated for their potential effects on outcome. This study also aims to review hops toxicosis and treatment options. Retrospective observational study. Poison Control Center. Seventy-one dogs presenting for hops ingestion. None. Records of 71 dogs with known hops ingestion from the ASPCA - Animal Poison Control Center (ASPCA-APCC) database and the Tufts University medical record system were reviewed. Fifty-nine (77%) of the dogs survived. The most common clinical signs on presentation were hyperthermia and tachycardia, with presenting temperatures and heart rates significantly higher in nonsurvivors. There was no significant difference between survivors and nonsurvivors in regard to signalment. Time to presentation was shorter in survivors (5.0 vs 5.5 h; P < 0.0001). The median amount of hops ingested was higher in nonsurvivors (2 vs 2.5 oz; P < 0.0001). Hops ingestion caused hyperthermia in 96% (68/71) of dogs. The median time to death in the nonsurvivor group was 10.7 hours (2-30 h). None of the decontamination, cooling, or treatment measures (dantrolene, cyproheptadine, sedatives) evaluated in this population were associated with improved survival. After adjusting for cooling, time to presentation, and dantrolene administration, every degree of elevation in temperature was associated with a 78% increased chance of death. All dogs that survived to discharge had complete resolution of clinical signs. Hops toxicosis can result in significant hyperthermia, tachypnea, and tachycardia. Seventy-seven percent of dogs survived with intensive treatment. Continued education of the potential for hops toxicosis is advised.


Species selectivity in poxviral complement regulators is dictated by the charge reversal in the central complement control protein modules.
Variola and vaccinia viruses, the two most important members of the family Poxviridae, are known to encode homologs of the human complement regulators named smallpox inhibitor of complement enzymes (SPICE) and vaccinia virus complement control protein (VCP), respectively, to subvert the host complement system. Intriguingly, consistent with the host tropism of these viruses, SPICE has been shown to be more human complement-specific than VCP, and in this study we show that VCP is more bovine complement-specific than SPICE. Based on mutagenesis and mechanistic studies, we suggest that the major determinant for the switch in species selectivity of SPICE and VCP is the presence of oppositely charged residues in the central complement control modules, which help enhance their interaction with factor I and C3b, the proteolytically cleaved form of C3. Thus, our results provide a molecular basis for the species selectivity in poxviral complement regulators.


SIMONI (smart integrated monitoring) as a novel bioanalytical strategy for water quality assessment: Part i-model design and effect-based trigger values.
It is virtually impossible to reliably assess water quality with target chemical analyses only. Therefore, a complementary effect-based risk assessment by bioanalyses on mixtures of bioavailable micropollutants is proposed: the Smart Integrated Monitoring (SIMONI) strategy. The goal of this strategy is to obtain more reliable information on the water quality to select optimum measures for improvement. The SIMONI strategy is 2-tiered. Tier 1 is a bioanalytical hazard identification of sites. A tier 2 ecological risk assessment is carried out only at a limited number of sites where increased hazards are detected in tier 1. Tier 2 will be customized, based on tier 1 evaluation and additional knowledge of the aquatic system. The present study focuses on the tier 1 bioanalytical hazard identification to distinguish "hot spots" of chemical pollution. First, a selection was made of relevant and cost-effective bioanalytical endpoints to cover a wide spectrum of micropollutant modes of action. Specific endpoints may indicate which classes of chemicals might cause adverse effects. Second, effect-based trigger values (EBT) were derived for these bioassays to indicate potential ecological risks. Comparison of EBT with bioassay responses should discriminate sites exhibiting different chemical hazards. Third, a model was designed to estimate the overall risks for aquatic ecosystems. The associated follow-up for risk management is a "toxicity traffic light" system: green, low hazard (no action required); orange, potential risk (further research needed); and red, high risk (mitigation measures). Thanks to cost-effectiveness, flexibility, and relevance, the SIMONI strategy has the potential to become the first bioanalytical tool to be applied in regular water quality monitoring programs. Environ Toxicol Chem 2017;36:2385-2399. © 2017 SETAC.


Pharmacological effects of ex vivo mesenchymal stem cell immunotherapy in patients with acute kidney injury and underlying systemic inflammation.
Mesenchymal stem cells (MSCs) have natural immunoregulatory functions that have been explored for medicinal use as a cell therapy with limited success. A phase Ib study was conducted to evaluate the safety and immunoregulatory mechanism of action of MSCs using a novel ex vivo product (SBI-101) to preserve cell activity in patients with severe acute kidney injury. Pharmacological data demonstrated MSC-secreted factor activity that was associated with anti-inflammatory signatures in the molecular and cellular profiling of patient blood. Systems biology analysis captured multicompartment effects consistent with immune reprogramming and kidney tissue repair. Although the study was not powered for clinical efficacy, these results are supportive of the therapeutic hypothesis, namely, that treatment with SBI-101 elicits an immunotherapeutic response that triggers an accelerated phenotypic switch from tissue injury to tissue repair. Ex vivo administration of MSCs, with increased power of testing, is a potential new biological delivery paradigm that assures sustained MSC activity and immunomodulation.


The relationships of attachment style and social maladjustment to death ideation in depressed women with a history of childhood sexual abuse.
The current study examined the interaction of attachment orientation and acute social maladjustment as risk factors for death ideation in a sample of women with Major Depression and histories of childhood sexual abuse. Social maladjustment was associated with greater endorsement of death ideation. Avoidant and anxious attachment orientations moderated the social maladjustment and death ideation associations in some domains. Work-related maladjustment was associated with greater odds of death ideation for those with higher attachment avoidance. Parent-role maladjustment was associated with greater odds of death ideation for those with lower attachment anxiety. Findings demonstrate strong associations between death ideation and social maladjustment, and suggest that death ideation may be specific to certain domains of adjustment for anxious and avoidant attachment styles.


Influence of encapsulation on phagocytosis of Pasteurella multocida by bovine neutrophils.
The effect of encapsulation on phagocytosis of Pasteurella multocida by bovine neutrophils was examined by using two encapsulated strains, NA77 (capsular type A) and C42 (capsular type B), and comparing them with an unencapsulated counterpart strain, 1173. The uptake of [(3)H]thymidine-labeled bacteria by neutrophils was quantitatively measured after incubation of the bacteria in normal bovine serum, heat-inactivated serum, and hyperimmune sera (anti-NA77 and anti-C42). Results showed that all three strains of P. multocida were ineffectively opsonized by the heat-labile serum complement system. The unencapsulated strain was completely phagocytized in the presence of heat-stable opsonins found in normal serum. Although encapsulation of strain C42 was found to interfere with opsonization by normal serum, this strain was completely phagocytized when hyperimmune serum (anti-C42) was used as the opsonin source. These results suggest that specific anticapsular antibodies found in the hyperimmune serum readily opsonized the encapsulated strain C42 and enhanced phagocytosis. The presence of a thick capsule on strain NA77 interfered with phagocytosis in the presence of normal or hyperimmune serum (anti-NA77). This interference was due to the presence of hyaluronic acid which was a major component of the capsule. Treatment of this encapsulated strain with hyaluronidase decapsulated the bacteria. Bacteria treated in this way were almost completely phagocytized (90%) in the presence of heat-stable opsonins. The exact mechanism by which the capsule of P. multocida NA77 interfered with phagocytosis was not demonstrated; perhaps the slimy nature of the hyaluronic acid makes the phagocytic act difficult by changing the physiochemical surface properties, or it may prevent opsonization.


Effect of binocular rivalry suppression on initial ocular following responses.
To study the effect of binocular rivalry (BR) suppression on the ocular following response (OFR), we recorded the OFR in both the suppressed and the dominant phases of BR. The BR was established using stationary horizontal/vertical grating patterns presented on two PC monitors. Once a subjective image of a vertical or horizontal grating pattern was perceived, subjects pressed a button to trigger an onset of brief horizontal movement (750 ms) of the vertical grating pattern and an offset of the horizontal pattern. The OFRs were recorded using a scleral search coil system at 1 kHz. The OFRs from the suppressed phases were significantly reduced compared to those from the dominant phases. The OFRs were asymmetrical to temporalward and nasalward motion in most conditions. We suggest that asymmetry of OFRs under the incomplete BR conditions may be a reflection of imbalance binocular inputs and processing in the visual system similar to asymmetrical optokinetic nystagmus in strabismic subjects. The latency of the OFR in deeper suppressed conditions was prolonged, suggesting that the interaction of BR and OFR may occur at multiple stages including an early stage of the visual processing. The OFR may have the potential for objective measurement of BR suppression in clinical evaluation of binocular function.


Fecal microbiota transplantation: Emerging applications in autoimmune diseases.
Both genetic susceptibility and environmental factors are important contributors to autoimmune disease pathogenesis. As an environmental factor, the gut microbiome plays a crucial role in the development and progression of autoimmune diseases. Thus, strategies targeting gut microbiome alterations can potentially be used to treat autoimmune disease. Microbiota-based interventions, such as prebiotics, probiotics, dietary interventions, and fecal microbiota transplantation (FMT), have attracted growing interest as novel treatment approaches. FMT is an effective method for treating recurrent Clostridioides difficile infections; moreover, it is emerging as a promising treatment for patients with inflammatory bowel disease and other autoimmune diseases. Although the mechanisms underpinning the interaction between the gut microbiome and host are not fully understood in patients with autoimmune disease, FMT has been shown to restore altered gut microbiota composition, rebuild the intestinal microecosystem, and mediate innate and adaptive immune responses to achieve a therapeutic effect. In this review, we provide an overview of FMT and discuss how FMT can be used as a novel treatment approach for autoimmune diseases. Furthermore, we discuss recent challenges and offer future research directions.


Protein sources of heme for Haemophilus influenzae.
Although Haemophilus influenzae requires heme for growth, the source of heme during invasive infections is not known. We compared heme, lactoperoxidase, catalase, cytochrome c, myoglobin, and hemoglobin as sources of heme for growth in defined media. The minimum concentration of heme permitting unrestricted growth of strain E1a, an H. influenzae type b isolate from cerebrospinal fluid, was 0.02 micrograms/ml. Using molar equivalents of heme as lactoperoxidase, catalase, cytochrome c, myoglobin, and hemoglobin, we determined that myoglobin and hemoglobin permitted unrestricted growth at this concentration. To determine the ability of host defenses to sequester heme from H. influenzae, we used affinity chromatography to purify human haptoglobin and hemopexin, serum proteins which bind hemoglobin and heme. Plate assays revealed that 12 strains of H. influenzae acquired heme from hemoglobin, hemoglobin-haptoglobin, heme-hemopexin, and heme-albumin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of outer membrane proteins of strain E1a grown in heme-replete and heme-restricted conditions revealed a heme-repressible outer membrane protein with an apparent molecular mass of 38 kilodaltons. These results demonstrated that, unlike Escherichia coli, H. influenzae may acquire heme from hemoglobin-haptoglobin. H. influenzae also may acquire heme from hemopexin and albumin, which have not been previously investigated. The role of outer membrane proteins in the acquisition of heme is not yet clear.


A dynamic attitude measurement system based on LINS.
A dynamic attitude measurement system (DAMS) is developed based on a laser inertial navigation system (LINS). Three factors of the dynamic attitude measurement error using LINS are analyzed: dynamic error, time synchronization and phase lag. An optimal coning errors compensation algorithm is used to reduce coning errors, and two-axis wobbling verification experiments are presented in the paper. The tests indicate that the attitude accuracy is improved 2-fold by the algorithm. In order to decrease coning errors further, the attitude updating frequency is improved from 200 Hz to 2000 Hz. At the same time, a novel finite impulse response (FIR) filter with three notches is designed to filter the dither frequency of the ring laser gyro (RLG). The comparison tests suggest that the new filter is five times more effective than the old one. The paper indicates that phase-frequency characteristics of FIR filter and first-order holder of navigation computer constitute the main sources of phase lag in LINS. A formula to calculate the LINS attitude phase lag is introduced in the paper. The expressions of dynamic attitude errors induced by phase lag are derived. The paper proposes a novel synchronization mechanism that is able to simultaneously solve the problems of dynamic test synchronization and phase compensation. A single-axis turntable and a laser interferometer are applied to verify the synchronization mechanism. The experiments results show that the theoretically calculated values of phase lag and attitude error induced by phase lag can both match perfectly with testing data. The block diagram of DAMS and physical photos are presented in the paper. The final experiments demonstrate that the real-time attitude measurement accuracy of DAMS can reach up to 20″ (1σ) and the synchronization error is less than 0.2 ms on the condition of three axes wobbling for 10 min.


Mid-Term Radiological and Functional Outcomes of Bicondylar Tibial Plateau Fractures Managed with Open Reduction and Internal Fixation Using Dual Plates.
This study aimed to evaluate the mid-term radiological and functional outcome of tibial plateau fractures treated by plating. This study was conducted at the General Hospital of Thessaloniki 'Papageorgiou', Thessaloniki, Greece. Patients with Schatzker type V and VI tibial plateau fractures who were managed with open reduction and internal fixation using dual plates between January 2011 and December 2018 were included in this retrospective study. The functional evaluation of the patients was carried out with the visual analogue scale (VAS), the health-related quality of life status was measured using the Short Form-36 and the dimensions of pain, stiffness and function were assessed using the Western Ontario and McMaster Universities Arthritis Index. For the radiological outcome evaluation, the modified Rasmussen criteria were used. Fifty-seven patients (30 male and 27 female) were included in the study with a mean follow-up of 50.88 months. There were 23 Schatzker type V and 34 type VI fractures. The majority of patients (86%) had a good to excellent radiological outcome. The mean VAS score was 1.65 for all the patients. The functional outcome was excellent in the majority of the patients. Among them, 5.3% (n = 3) suffered wound infection and all wounds healed after different treatments. All patients returned to their pre-injury activities of daily living and employment status, while 53% of the patients returned to sporting activities. The findings support previous literature which has demonstrated that bicondylar tibial plateau fractures can provide good-to-excellent radiological and functional outcomes if they are treated with open reduction and internal fixation with dual plating.


Characteristic tissue interaction of the diastema region in mice.
Rodents have a toothless diastema between the incisor and the first molar, which may contain rudimentary tooth germs. In the lower diastema region of mice at E13, the rudimentary tooth germs, which developed into the bud stage before its removal by apoptosis, was found. The immunoreactivity to tenascin was observed in the condensed mesenchyme around the normal tooth bud and was detected in only the basement membrane in the diastema bud. This result shows that the relationship between mesenchymal condensation and tooth development. The similar patterns of Msx-1 and Msx-2 expression between the tooth bud and the diastema bud show that the diastema bud may have some other genetic mechanism in the developmental arrest of the rudimentary tooth germs rather than the Msx-1 and Msx-2 expression. Strikingly, the induction of the tooth formation was possible using tissue recombination between the oral epithelium of the diastema bud and the dental mesenchyme of the molar tooth bud, which indicates the potential capability of the diastema in the tooth formation. In conclusion, it is suggested that the condensed mesenchyme may be the key to tooth development.


Metabolic factors and the risk of small intestine cancers: Pooled study of 800 000 individuals in the metabolic syndrome and cancer project.
To explore the largely unknown etiology of small intestine cancer, we examined metabolic factors and risk of small intestine cancer overall and by subtypes. Among 404 220 women and 403 265 men in six European cohorts, we applied Cox regression with adjustment for smoking and body mass index (BMI), to calculate sex-specific hazard ratios (HRs) of small intestine cancer by levels of BMI, mean arterial pressure (MAP) and plasma total cholesterol, triglycerides and glucose. We also calculated HRs for these factors combined (metabolic score; MetS) and used Wald test statistics to investigate pairwise interactions between metabolic factors on risk. We also performed analyses separately per subtype (neuroendocrine tumors [NETs] and adenocarcinomas). During a median follow-up of 16.9 years, 144 women and 195 men were diagnosed with small intestine cancer, including 184 NETs and 99 adenocarcinomas. Among men, no main associations or interactions between metabolic factors were observed in relation to the risk of small intestine cancer. Among women, triglycerides were positively and linearly associated with risk (HR per standard deviation [SD]: 1.23, 95% confidence interval [CI]: 1.04-1.46), and a positive association was also observed for the MetS (HR per SD: 1.25, 95% CI: 1.02-1.52). Positive interactions were observed among women between triglycerides and cholesterol (P = .0005), and between MAP and glucose (P = .009), on risk. Glucose was positively associated with adenocarcinomas among women. This large, prospective study suggests that elevated triglycerides, and metabolic factors in interaction, confer an increased risk of small intestine cancer among women, but not among men.


High resolution crystal structure of pyruvate decarboxylase from Zymomonas mobilis. Implications for substrate activation in pyruvate decarboxylases.
The crystal structure of tetrameric pyruvate decarboxylase from Zymomonas mobilis has been determined at 1.9 A resolution and refined to a crystallographic R-factor of 16.2% and Rfree of 19.7%. The subunit consists of three domains, all of the alpha/beta type. Two of the subunits form a tight dimer with an extensive interface area. The thiamin diphosphate binding site is located at the subunit-subunit interface, and the cofactor, bound in the V conformation, interacts with residues from the N-terminal domain of one subunit and the C-terminal domain of the second subunit. The 2-fold symmetry generates the second thiamin diphosphate binding site in the dimer. Two of the dimers form a tightly packed tetramer with pseudo 222 symmetry. The interface area between the dimers is much larger in pyruvate decarboxylase from Z. mobilis than in the yeast enzyme, and structural differences in these parts result in a completely different packing of the subunits in the two enzymes. In contrast to other pyruvate decarboxylases, the enzyme from Z. mobilis is not subject to allosteric activation by the substrate. The tight packing of the dimers in the tetramer prevents large rearrangements in the quaternary structure as seen in the yeast enzyme and locks the enzyme in an activated conformation. The architecture of the cofactor binding site and the active site is similar in the two enzymes. However, the x-ray analysis reveals subtle but significant structural differences in the active site that might be responsible for variations in the biochemical properties in these enzymes.