Community structure and functional diversity of the plastisphere in aquaculture waters: Does plastic color matter?
Microplastics (MPs) serve as a niche for colonization of biofilm-forming microorganisms, termed as plastisphere. Distinct microbial assemblages between MPs and surrounding waters have been well reported, but little is known about driving factors affecting biofilm development on plastic surfaces. Here, to investigate the influence of plastic colors on microbial assemblages, we performed a biofilm incubation experiment, in an aquaculture pond, using MPs in colors (blue, yellow and transparent) that commonly found in the aquatic environments for 30 days. We examined the community structure and function of plastisphere by using 16S rRNA sequencing. The results showed that plastisphere communities exhibited a higher diversity and evenness compared with the water community. MPs especially the blue MPs had more unique species, which might indicate a plastic color/additive-driven selection of microorganisms on MPs. A significant distinctness in bacterial community composition between MPs and the water was found, mainly caused by large amounts of Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium but trace amounts of Microcystis_PCC-7914 on MPs. Due primarily to rich in Aquabacterium but lack of norank_f__norank_o__1-20 on blue MPs than on transparent and yellow MPs, a clear separation between plastisphere communities of three colors of MPs was also observed. Moreover, compared with the water column, the metabolic pathways, e.g., transport and metabolism of amino acid, carbohydrate and inorganic ion, on plastisphere especially those of blue MPs were generally enriched. Biofilms colonizing on blue MPs appeared to have a higher functional diversity than those on transparent or yellow MPs. These results might suggest that plastic colors have impacts on the community structure and functional diversity of plastisphere.


Different beta-subunits determine G-protein interaction with transmembrane receptors.
Regulatory GTP-binding proteins (G proteins) are membrane-attached heterotrimers (alpha, beta, gamma) that mediate cellular responses to a wide variety of extracellular stimuli. They undergo a cycle of guanine-nucleotide exchange and GTP hydrolysis, during which they dissociate into alpha-subunit and beta gamma complex. The roles of G-protein alpha-subunits in these processes and for the specificity of signal transduction are largely established; the beta- and gamma-subunits are essential for receptor-induced G-protein activation and seem to be less diverse and less specific. Although the complementary DNAs for several beta-subunits have been cloned, isolated subunits have only been studied as beta gamma complexes. Functional differences have been ascribed to the gamma-subunit on the basis of extensive sequence similarity among beta-subunits and apparent heterogeneity in gamma-subunit sequences. Beta gamma complexes can interact directly or indirectly with different effectors. They seem to be interchangeable in their interaction with pertussis toxin-sensitive alpha-subunits, so we tested this by microinjecting antisense oligonucleotides into nuclei of a rat pituitary cell line to suppress the synthesis of individual beta-subunits selectively. Here we show that two out of four subtypes of beta-subunits tested (beta 1 and beta 3) are selectively involved in the signal transduction cascades from muscarinic M4 (ref. 4) and somatostatin receptors, respectively, to voltage-dependent Ca2+ channels.


Novel techniques for drug loading quantification in mesoporous SBA-15 using chemometric-assisted UV and FT-IR data.
Albendazole is a crystalline drug that is poorly soluble in water, thus the dissolution rate in gastrointestinal fluids is limited. Mesoporous materials loaded with poorly water-soluble drugs become an interesting strategy to increase their solubility/dissolution rate as the drug state changes from crystalline to amorphous. In order to determine the drug loading content into mesoporous materials analytical methods such as elemental analysis, UV and HPLC are commonly used. However, elemental analysis and HPLC are destructive and relatively expensive. In addition, UV is time consuming. Moreover, UV and HPLC require the drug release from the mesoporous material before the quantification step. Therefore, the aim of this work was to develop quantifications techniques based on chemometric models combined with UV and FT-IR spectra without needing the drug release from the mesoporous material. Partial least squares regression (PLSR) was used as chemometric regression method. Albendazole content in the SBA-15 powders was first quantified by elemental analysis as reference measurement for multivariate calibration. The excellent drug loading predictions prove that robust calibration models can be obtained from both techniques (i.e., 0.999 and 0.998 adjusted correlation coefficient for UV and FT-IR, respectively). Additionally, the adjusted correlation coefficients determined from the validation models for UV and FT-IR are 0.963 and 0.930, respectively. It is important to highlight that the prediction adjustment of the FT-IR model (root-mean-square error of prediction=2.196%) presented lower error than the UV model (root-mean-square error of prediction=3.553%). Therefore, this development contributes to improve the overall time and cost of drug loading determination into mesoporous materials.


Tissue distribution and excretion of radioactively labelled compounds in the Wistar rat after administration of [N-methyl-14C]-erythromycin A.
Tissue distribution and excretion of radioactively labelled compounds was studied in the Wistar rat after i.v. administration of [N-methyl-14C]-erythromycin A. Whole-body autoradiography and liquid scintillation counting was used to investigate the tissue localization of radioactivity in pregnant and non-pregnant rats. Tissue levels were maximal within 20 min, except for lachrymal glands, thymus and brain. Large amounts of radioactively labelled compounds, partly originating from active secretion, were present in the small intestine and caecum. Marked concentration of radioactively labelled compounds was also observed in the liver, spleen, lachrymal and salivary glands, lymph nodes, mammary glands, skin, bone marrow, and, to a lesser extent, in the lung, kidney and skeletal muscle. During six hours of experimental follow-up, plasma levels remained lower than corresponding tissue levels. At 1 h the radioactivity in fetuses was about three times lower than that in maternal blood. Within 48 h, more than 90% of the administered radioactivity was excreted. The amounts of radioactivity recovered in urine, faeces and expired air were about 19%, 48% and 24% respectively. After 48 h, 8% of the administered radioactivity was found in the carcass.


Five questions about Streptococcus mutans: theoretical study of its transmission and colonisation.
This theoretical study aimed to identify the decisive (and controllable) factors involved in Streptococcus mutans (Sm) infection through addressing questions about (i) the time and prevalence pattern (including the raison d'etre of the discrete period for the infection or WI) of initial Sm colonisation and (ii) the infant's selection of bacterial types and their diversity, which are not yet definitely answered by empirical works. A model of Sm infection (within-host type) was developed. For questions (i): using the basic model, stochastic simulation was performed to reproduce longitudinal observations of the initial colonisation time. A symmetrical or right-skewed gamma distribution was assumed for the maximum colonisable area (K(max)) and transmission rate (mx). Additionally, 3 or 4 developmental modes of colonisable area [K(t)] were assigned based on the K(max) value. For (ii): by extending the basic model to the two-bacterial type model, intraspecific competition analysis focusing on the differences in mx (received by the infancy) and colonisation ability (θD) was performed. The basic model simulation showed that mx and K(t) played a pivotal role in determining the individual time of initial colonisation and their variations among infants in forming its prevalence patterns (with or without WI). The competition model simulation showed that higher mx could be more advantageous in competitive colonisation than higher θD under repeated invasions. Accordingly, it played a decisive role in infant's selection of initially, persistently and transiently colonising bacterial types, and thus in their diversity. (i) The mx is the primary and controllable (risk) factor that extensively affects various aspects of the Sm infection process. (ii) Also, the growing carrying capacity, i.e., K(t) is another important factor when considering how to effectively delay the onset of the colonisation. (iii) Thus, currently, the most feasible and effective control measure for the infection should be microbiological interventions in the primary host with concurrent oral hygiene and dietary control in the exposed child.


Oligosaccharyltransferase isoforms that contain different catalytic STT3 subunits have distinct enzymatic properties.
Oligosaccharyltransferase (OST) is an integral membrane protein that catalyzes N-linked glycosylation of nascent proteins in the lumen of the endoplasmic reticulum. Although the yeast OST is an octamer assembled from nonhomologous subunits (Ost1p, Ost2p, Ost3p/Ost6p, Ost4p, Ost5p, Wbp1p, Swp1p, and Stt3p), the composition of the vertebrate OST was less well defined. The roles of specific OST subunits remained enigmatic. Here we show that genomes of most multicellular eukaryotes encode two homologs of Stt3p and mammals express two homologs of Ost3p. The Stt3p and Ost3p homologs are assembled together with the previously described mammalian OST subunits (ribophorins I and II, OST48, and DAD1) into complexes that differ significantly in enzymatic activity. Tissue and cell type-specific differences in expression of the Stt3p homologs suggest that the enzymatic properties of oligosaccharyltransferase are regulated in eukaryotes to respond to alterations in glycoprotein flux through the secretory pathway and may contribute to tissue-specific glycan heterogeneity.


Monolingual and bilingual children's performance on arithmetic fluency varies by language fluency.
Research has demonstrated that learning two or more languages during development (i.e., becoming bilingual) shapes children's cognition in myriad ways. However, because such studies have largely been conducted using laboratory experiments, it is unclear how bilingualism may modulate more naturalistic cognitive skills such as arithmetic fluency. Moreover, how the relationship between speaking two (or more) languages and arithmetic varies with language fluency-specifically, the degree of bilingualism-has been understudied. Therefore, this study examined third- to fifth-grade monolingual (n = 70) and bilingual (n = 51) children's performance on an arithmetic fluency task. Monolinguals' and bilinguals' performance on the arithmetic fluency task did not differ. However, individual differences in the relation between children's arithmetic fluency and their language fluency were found, suggesting that bilingual children's skill in their nondominant language was associated with arithmetic fluency. These findings point to the importance of examining individual differences in language fluency among bilinguals to understand how bilingualism may shape cognitive skills.


Histone acetylation and gene induction in human cells.
An antibody recognising acetylated core histones was used to immunoprecipitate chromatin fragments from proliferating human K562 cells and from cells induced to differentiate with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). The DNA of the acetylated chromatin was probed with sequences of platelet derived growth factor B chain (PDGF-B), a gene which is induced to strong expression upon differentiation. A high level of acetylation was observed before gene induction and no change seen following induction. This implies that core histone acetylation is an essential precondition for transcription.


Determinants of thermal balance in the Hawaiian giant rosette plant, Argyroxiphium sandwicense.
The effects of leaf pubescence and rosette geometry on thermal balance were studied in a subspecies of a Hawaiian giant rosette plant, Argyroxiphium sandwicense. This species, a member of the silversword alliance, grows above 2000 m elevation in the alpine zone of two Hawaiian volcanoes. Its highly pubescent leaves are very reflective (absorptance in the 400-700 nm waveband=0.44). Temperature of the expanded leaves was very similar to, or even lower than, air temperature during clear days, which was somewhat surprising given that solar radiation at the high elevation sites where this species grows can exceed 1100 W m-2. However, the temperature of the apical bud, which is located in the center of the parabolic rosette, was usually 25°C higher than air temperature at midday. Experimental manipulations in the field indicated that incoming solar radiation being focussed towards the center of the rosette resulted in higher temperatures of the apical bud. Attenuation of wind speed inside the rosette, which increased the thickness of the boundary layer surrounding the apical bud, also contributed to higher temperatures. The heating effect on the apical bud of the large parabolic rosette, which apparently enhances the rates of physiological processes in the developing leaves, may exclude the species from lower elevations by producing lethal tissue temperatures. Model simulations of apical bud temperatures at different elevations and laboratory estimates of the temperature threshold for permanent heat injury predicted that the lower altitude limit should be approximately 1900 m, which is reasonably close to the lower limit of distribution of A. sandwicense on Haleakala volcano.


Human TFIID binds to core promoter DNA in a reorganized structural state.
A mechanistic description of metazoan transcription is essential for understanding the molecular processes that govern cellular decisions. To provide structural insights into the DNA recognition step of transcription initiation, we used single-particle electron microscopy (EM) to visualize human TFIID with promoter DNA. This analysis revealed that TFIID coexists in two predominant and distinct structural states that differ by a 100 Å translocation of TFIID's lobe A. The transition between these structural states is modulated by TFIIA, as the presence of TFIIA and promoter DNA facilitates the formation of a rearranged state of TFIID that enables promoter recognition and binding. DNA labeling and footprinting, together with cryo-EM studies, were used to map the locations of TATA, Initiator (Inr), motif ten element (MTE), and downstream core promoter element (DPE) promoter motifs within the TFIID-TFIIA-DNA structure. The existence of two structurally and functionally distinct forms of TFIID suggests that the different conformers may serve as specific targets for the action of regulatory factors.


Multiple primary tumours in a population-based series of patients with histopathologically peer-reviewed sarcomas.
Multiple primary tumours occurring in a three-year population-based series of patients with histopathologically peer-reviewed sarcomas from North West England were ascertained in order to look at the patterns of neoplasms seen. A total of 30 out of the 310 patients entered in the study had additional primary tumours. Very few patients were aged under 60 years at diagnosis of both their malignancies. The youngest was a known case of neurofibromatosis and, although seven patients were diagnosed with a sarcoma and carcinoma of the breast--a combination of cancers characteristic of the Li-Fraumeni cancer family syndrome--no other patients could directly be identified as suffering from any other cancer predisposition syndrome.


Controlled Fabrication of K2Ti8O17 Nanowires for Highly Efficient and Ultrafast Adsorption toward Methylene Blue.
Advanced adsorbents need high adsorption rate and superior adsorption capability to clean up organic methylene blue (MB) from wastewater. We prepared K2Ti8O17 nanowires grown along the [0 1 0] direction with a one-step hydrothermal method. The K2Ti8O17 nanowires with tens of nanometers in diameter and tens of micrometers in length were achieved with smooth surfaces and twisted wire-like morphology. The K2Ti8O17 nanowires exhibit high uptake capacity of ∼208.8 mg·g-1 in the MB removal under equilibrium pH = 7. The adsorption equilibrium of MB onto the K2Ti8O17 adsorbent is achieved with a 97% removal rate of MB within only ∼21 min, which is the shortest adsorption time among the recently reported inorganic adsorbents toward MB. The adsorption process has a good agreement with the well-known pseudo-second-order kinetic model (k2 = 0.2) and the Langmuir isotherm model. Fourier transform infrared measurements suggest that the adsorption can be assigned to the hydrogen bonding and electrostatic attraction between MB and K2Ti8O17. This ultrafast removal ability is due to the larger (0 2 0) interplanar spacing and zigzag surface structure of the nanowires, which provide abundant active adsorption sites. Thermodynamic parameters reflect the spontaneous, exothermic, and feasible uptake of MB. Besides, K2Ti8O17 nanowires enjoy high adsorptive ability for chromium(VI) ions and photocatalytic removal toward NO. This work highlights the great significance of K2Ti8O17 nanowires as a low-cost promising material used for the adsorptive elimination of organic contaminations in fast water purification on a large scale.


Comparison of the equilibrium exchange of nucleosides and 3-O-methylglucose in human erythrocytes and of the effects of cytochalasin B, phloretin and dipyridamole on their transport.
Because of similarities in the physical and molecular properties of the nucleoside and sugar transporters of human erythrocytes and the photoaffinity labeling of the sugar transporter by 8-azidoadenosine (Jarvis et al. (1986) J. Biol. Chem. 261, 11077-11085), we have directly compared the equilibrium exchange of uridine and 3-O-methylglucose in these cells as measured by rapid kinetic techniques under identical experimental conditions. Both the Michaelis-Menten constant and maximum velocity were about 100-fold higher for 3-O-methylglucose exchange than for uridine exchange so that the first order rate constants for both transporters were about the same. When calculated on the basis of the number of nucleoside and sugar carriers per red cell estimated by equilibrium binding of nitrobenzylthioinosine and cytochalasin B, respectively, the turnover numbers for the sugar and nucleoside carriers with 3-O-methylglucose and uridine, respectively, as substrates were quite similar. Various sugars up to concentrations of 108 mM had no effect on the exchange of 500 microM uridine or adenosine, and uridine up to a concentration of 50 mM had no effect on the exchange of 10 mM 3-O-methylglucose. Adenosine, on the other hand, inhibited 3-O-methylglucose exchange in a concentration dependent manner, though not very effectively (IC50 approximately equal to 3 mM). Both uridine and 3-O-methylglucose exchange were inhibited in a concentration dependent manner by cytochalasin B, phloretin and dipyridamole, but cytochalasin B and phloretin were 100-times more effective in inhibiting 3-O-methylglucose than uridine exchange, whereas the opposite was the case for the inhibition by dipyridamole.


Influence of social factors on the relation between lie-telling and children's cognitive abilities.
Lie-telling may be part of a normative developmental process for children. However, little is known about the complex interaction of social and cognitive factors related to this developmental behavior. The current study examined parenting style, maternal exposure to stressors, and children's cognitive abilities in relation to children's antisocial lie-telling behavior in an experimental setting. Children (3-6years, N=157) participated in a modified temptation resistance paradigm to elicit spontaneous lies. Results indicate that high authoritative parenting and high inhibitory control interact to predict a lower propensity to lie, but those who did lie had better semantic leakage control. This suggests that although children's lie-telling may be normative during early development, the relation to children's cognitive abilities can be moderated by responsive parenting behaviors that discourage lying.


Fish to meat intake ratio and cooking oils are associated with hepatitis C virus carriers with persistently normal alanine aminotransferase levels.
Dietary habits are involved in the development of chronic inflammation; however, the impact of dietary profiles of hepatitis C virus carriers with persistently normal alanine transaminase levels (HCV-PNALT) remains unclear. The decision-tree algorithm is a data-mining statistical technique, which uncovers meaningful profiles of factors from a data collection. We aimed to investigate dietary profiles associated with HCV-PNALT using a decision-tree algorithm. Twenty-seven HCV-PNALT and 41 patients with chronic hepatitis C were enrolled in this study. Dietary habit was assessed using a validated semiquantitative food frequency questionnaire. A decision-tree algorithm was created by dietary variables, and was evaluated by area under the receiver operating characteristic curve analysis (AUROC). In multivariate analysis, fish to meat ratio, dairy product and cooking oils were identified as independent variables associated with HCV-PNALT. The decision-tree algorithm was created with two variables: a fish to meat ratio and cooking oils/ideal bodyweight. When subjects showed a fish to meat ratio of 1.24 or more, 68.8% of the subjects were HCV-PNALT. On the other hand, 11.5% of the subjects were HCV-PNALT when subjects showed a fish to meat ratio of less than 1.24 and cooking oil/ideal bodyweight of less than 0.23 g/kg. The difference in the proportion of HCV-PNALT between these groups are significant (odds ratio 16.87, 95% CI 3.40-83.67, P = 0.0005). Fivefold cross-validation of the decision-tree algorithm showed an AUROC of 0.6947 (95% CI 0.5656-0.8238, P = 0.0067). The decision-tree algorithm disclosed that fish to meat ratio and cooking oil/ideal bodyweight were associated with HCV-PNALT.


Change of extracellular glutamate and gamma-aminobutyric acid in substantia nigra and globus pallidus during electrical stimulation of subthalamic nucleus in epileptic rats.
To study the neurochemical change during high-frequency stimulation of the subthalamic nucleus in epileptic rats. Two animal groups - 12 rats with epilepsy induced by the systemic administration of kainic acid and 12 normal rats - were used. Concentric bipolar electrodes were stereotaxically implanted in the unilateral subthalamic nucleus (STN), stimulated by high frequencies of 130 and 260 Hz in each group. The microdialysis probes were unilaterally lowered into the globus pallidus (GP) and the substantia nigra pars reticulata (SNr). The concentrations of glutamate (Glu) and gamma-aminobutyric acid (GABA) in dialysate samples were determined by high-performance liquid chromatography. Electrical stimulation of the STN induced increases in GABA content in the SNr of each group, while GABA remained stable in the GP. The extracellular GABA level in the epileptic group was significantly higher than that of the normal group. In addition, the frequency of 130 Hz provoked the maximum increase in Glu contents both in the GP and SNr, whereas 260 Hz had less effect. This study demonstrates the neurochemical modifications in STN targets during electrical STN stimulation and shows that different frequencies of high-frequency stimulation have different effects on the neurotransmitters.


Effects of methylphenidate on cardiovascular responses in attention deficit hyperactivity disordered adolescents.
The short-term dose effects of methylphenidate were examined on cardiovascular measures in 11 black male adolescents diagnosed as having attention deficit hyperactivity disorder (ADHD). In a double-blind, cross-over design with randomized order, the subjects received placebo and each of three methylphenidate doses (0.15, 0.3, and 0.5 mg/kg) for a period of 2 weeks per medication dosage. Significant main effects were found for diastolic and systolic blood pressure; however, pairwise comparisons revealed a significant linear increase in diastolic blood pressure only. Because of the unexpected increase in diastolic blood pressure, careful monitoring of black adolescents who are receiving methylphenidate is recommended.


Increased myocardial mass and attenuation of myocardial strain in professional male soccer players and competitive male triathletes.
The purpose of this prospective study was to analyze the relationship between ventricular morphology and parameters of cardiac function in two different athletic groups and controls, using feature tracking cardiac magnetic resonance (FT-CMR). Twenty-three professional soccer players (22 ± 4 years), 19 competitive triathletes (28 ± 6 years) and 16 controls (26 ± 3 years) were included in the study. CMR was performed using a 1.5 T scanner. Cardiac chamber volumes, mass and biventricular global myocardial strain were obtained and compared. In comparison to the control subjects, athletes were characterized by a higher cardiac volume (p < 0.0001), higher cardiac mass (p < 0.001), reduced longitudinal strain of the left and right ventricle (p < 0.05 and p < 0.01 respectively) and reduced left ventricular radial strain (p < 0.05). Soccer players revealed higher amounts of left ventricular mass (87 ± 15 vs. 75 ± 13 g/m2, p < 0.05) than triathletes. Moreover, they showed a greater decrease in left and right ventricular longitudinal strain (p < 0.05 and p < 0.05) as well as in radial left ventricular strain (p < 0.05) in comparison to triathletes. An increase in left ventricular mass correlated significantly with a decrease in longitudinal (r = 0.47, p < 0.001) and radial (r = - 0.28, p < 0.05) strain. In athletes, attenuation of strain values is associated with cardiac hypertrophy and differ between soccer players and triathletes. Further studies are needed to investigate whether it is an adaptive or maladaptive change of the heart induced by intense athletic training.


Body weight gain in rats consuming sweetened liquids. Effects of caffeine and diet composition.
Previous studies show that high-intensity sweeteners can stimulate weight gain in rats. The present studies examined whether caffeine, a stimulant commonly added to beverages consumed by humans, influences intake of saccharin- or glucose-sweetened solutions or body weight gain in rats and whether the nature of the maintenance diet influences the effects of caffeine. In two experiments, rats received glucose or saccharin solution mixed with 0.125 mg/g caffeine or no caffeine. Rats consumed significantly more caffeinated than noncaffeinated solutions when they were maintained on a low-fat chow diet (Experiment 1) and when maintained on a sweet, high-fat, high calorie chow diet (Experiment 2). Consumption of saccharin resulted in higher body weight gain in both experiments. Caffeine reversed this effect in Experiment 1 (low-fat diet) but not Experiment 2 (sweet, high-fat diet). The findings extend what is known about the conditions under which consumption of high intensity sweeteners promote energy dysregulation.


Similarities and differences between anonymous and directed candidates for oocyte donation.
To compare anonymous and directed candidates for oocyte donation within a single program. 75 consecutive candidates for oocyte donation (49 anonymous and 26 directed) were studied using a semistructured interview to collect data on demographics, psychosocial history, motivation, and candidate views on disclosure to a potential child. Donor groups were similar with regard to race, religion and education. Anonymous donors (mean age 27.33 years, SD 4.17) were significantly younger than directed donors (mean age 37.54 years, SD 4.94), (t = -4.83, df = 73, p < 0.001). Marital duration was significantly longer for directed donors (6.92 years, SD 5.64) versus (2.57 years, SD 3.96) for anonymous donors (t = -3.50, df = 38.47, p = .001). Forty-one percent of anonymous and 69% of directed donors had previous pregnancies (X2 = 4.60, p < .05). A greater percentage of anonymous donors (34.7%) felt that the potential child should be informed of his or her origins, compared to 19% of directed donors, but this difference fell short of statistical significance. There were more similarities than differences among groups of potential donors with the exception of age, marital status, and previous pregnancies. Differing views about disclosure were suggested in both groups with anonymous donors tending to opt for disclosure.


The widespread myofascial pain of fibromyalgia is sympathetically maintained and immune mediated.
The recent demonstration of antibody-induced passive transfer of pain hypersensitivity from fibromyalgia (FM) subjects to mice brings renewed focus to the role of the immune system in generating FM pain. However, this data must be interpreted in the context of known myofascial pathology in FM, which includes impaired muscle relaxation and elevated intramuscular pressure. In addition, FM fascial biopsies demonstrate elevated inflammatory and oxidative stress markers and increased endomysial collagen deposition. This article proposes a unifying hypothesis for FM pain generation that connects known muscle and fascia abnormalities with the newly discovered role of antibodies. FM is characterized by persistent sympathetic nervous system hyperactivity which results in both pathologic muscle tension and an impaired tissue healing response. Although autoantibodies play a key role in normal tissue healing, sympathetic nervous system hyperactivity impairs the resolution of inflammation, and promotes autoimmunity and excessive autoantibody production. These autoantibodies can then bind with myofascial-derived antigen to create immune complexes, which are known to trigger neuronal hyperexcitability in the dorsal root ganglion. These hyperexcited sensory neurons activate the surrounding satellite glial cells and spinal microglia leading to pain hypersensitivity and central sensitization. Although immune system modulation may become an important treatment tool in FM, direct manual treatments that lessen myofascial inflammation and tension must not be neglected. Myofascial release therapy significantly reduces FM pain, with residual benefits even after the conclusion of treatment. Self-myofascial release techniques and gentle stretching programs also ease fibromyalgia pain, as do trigger point injections and dry-needling.


Association between admission biomarkers and clinical outcome in older adults diagnosed with an infection in the emergency department.
In older adults, prognostic performances of admission biomarkers have been poorly investigated. This study aims to compare the prognostic abilities of usual admission biomarkers, especially PCT and CRP, for major clinical outcomes, comparing older to younger adults diagnosed with an infection in the ED, and to investigate the prognostic abilities of PCT and CRP depending on the glomerular filtration rate (GFR). It was an observational, single-center, retrospective study, conducted in the Reims University Hospital, France. Endpoints were bacteremia, septic shock, and in-hospital mortality, related to the same ED visit. Over 1 year, 852 patients were included with 291 (34.2%) ≥75 years, and 127 (15.3%) patients had a GFR <30 mL.min-1.1.73 m2. Overall, 74 bacteremia, 56 septic shock and 82 in-hospital deaths have been observed. Prognostic abilities of admission biomarkers tended to be systematically lower in older compared to younger adults (PCT and CRP AUROC for bacteremia were, respectively, 0.71 and 0.62 in older adults vs 0.75 and 0.70 in younger adults; PCT and CRP AUROC for septic shock were, respectively, 0.71 and 0.66 in older adults vs 0.82 and 0.68 in younger adults). PCT showed a significant discriminating power for septic shock and in-hospital mortality only for GFR ≥ 30, and CRP showed a significant discriminating power for bacteremia and septic shock only for GFR ≥60. Caution must be taken when interpreting admission biomarkers, as their prognostic abilities are lower in older adults or in patients with renal insufficiency diagnosed with an infection.


Development of a promising fish model (Oryzias melastigma) for assessing multiple responses to stresses in the marine environment.
With the increasing number of contaminants in the marine environment, various experimental organisms have been "taken into labs" by investigators to find the most suitable environmentally relevant models for toxicity testing. The marine medaka, Oryzias melastigma, has a number of advantages that make it a prime candidate for these tests. Recently, many studies have been conducted on marine medaka, especially in terms of their physiological, biochemical, and molecular responses after exposure to contaminants and other environmental stressors. This review provides a literature survey highlighting the steady increase of ecotoxicological research on marine medaka, summarizes the advantages of using O. melastigma as a tool for toxicological research, and promotes the utilization of this organism in future studies.


Hospital-acquired complications: the relative importance of hospital- and patient-related factors.
To quantify the prevalence of hospital-acquired complications; to determine the relative influence of patient- and hospital-related factors on complication rates. Retrospective analysis of administrative data (Integrated South Australian Activity Collection; Victorian Admitted Episodes Dataset) for multiple-day acute care episodes for adults in public hospitals. Thirty-eight major public hospitals in South Australia and Victoria, 2015-2018. Hospital-acquired complication rates, overall and by complication class, by hospital and hospital type (tertiary referral, major metropolitan service, major regional service); variance in rates (intra-class correlation coefficient, ICC) at the patient, hospital, and hospital type levels as surrogate measures of their influence on rates. Of 1 558 978 public hospital episodes (10 029 918 bed-days), 151 486 included a total of 214 286 hospital-acquired complications (9.72 [95% CI, 9.67-9.77] events per 100 episodes; 2.14 [95% CI, 2.13-2.15] events per 100 bed-days). Complication rates were highest in tertiary referral hospitals (12.7 [95% CI, 12.6-12.8] events per 100 episodes) and for episodes including intensive care components (37.1 [95% CI, 36.7-37.4] events per 100 episodes). For all complication classes, inter-hospital variation was determined more by patient factors (overall ICC, 0.55; 95% CI, 0.53-0.57) than by hospital factors (ICC, 0.04; 95% CI, 0.02-0.07) or hospital type (ICC, 0.01; 95% CI, 0.001-0.03). Hospital-acquired complications were recorded for 9.7% of hospital episodes, but patient-related factors played a greater role in determining their prevalence than the treating hospital.


Broth dilution minimum inhibitory concentrations: rationale for use of selected antimicrobial concentrations.
A microdilution susceptibility testing procedure utilizing selected, clinically relevant concentrations of a large number of antimicrobial agents is described. A qualitative code designed to facilitate interpretation of quantitative results is coupled with each antimicrobial concentration. Both the antimicrobial concentrations selected for testing and the assigned codes are based on published data regardling attainable antimicrobial levels in serum and urine.


Aqueous humor pH changes after experimental alkali burns.
Following application of 2N sodium hydroxide, or 8.1N ammonium hydroxide to rabbit cornea, the aqueous humor pH reached a maximum of 10.2, 11.9, and 12 within six minutes following 20-, 50-, and 100-mu1 sodium hydroxide burns, respectively; after two hours the pH had fallen to 8.5, 10, and 10.5. The maximum rise following application of 100-mu1 of ammonium hydroxide was 10.8, declining to about 9 at two hours. The fall in pH following a 100-mu1 sodium hydroxide burn was not greatly influence by external lavage. However, the pH was significantly lowered (12 to 10) by paracentesis alone and further reduced by immediate or delayed intracameral administration of phosphate buffer. On the basis of these results moderately severe and severe alkali burns of the eye should be treated by paracentesis and if possible with anterior chamber reformation with a sterile solution.


Hierarchically porous carbon derived from potassium-citrate-loaded poplar catkin for high performance supercapacitors.
A simple one-step preparation of biomass derived carbon materials with hierarchical pore structure for supercapacitor application is proposed. Briefly, potassium citrate is loaded onto poplar catkin, a forestry and agricultural residue, for carbonization at different temperature (750-900 ℃). With the confined effect of poplar catkin and pore-forming role of potassium compounds, interconnected carbon networks combining of macropores, small mesopores and micropores are obtained. The product carbonized at 850 ℃ (S-850) processes large surface area of 2186 m2/g with two main micropore ranges distributed in 0.5-0.7 nm and 0.7-1.5 nm, and the sample of S-900 processes relatively high electrical conductivity because of the high degree of graphitization. The electrodes based on these carbon materials show main electrical double-layer capacitors with small part of pseudo-capacitors due to O-doping. The S-850 sample displays superior specific capacity at low charge-discharge current density while the electrode based on S-900 shows high specific capacity under high current density. The symmetrical devices based on S-850 give a superb stability and high energy and power densities in alkaline electrolyte. Within a voltage window of 1.4 V, the device can deliver a 13.3 Wh/kg energy density at a power density of 720 W/kg and maintain 7.8 Wh/kg at 14040 W/kg.


CYP450 biosensors based on gold chips for antiepileptic drugs determination.
Three-electrode configuration chips containing a Pt, Au and a screen-printed Ag/AgCl as counter, working and reference electrode, respectively, have been developed. Selective determination of Phenobarbital (PB) has been carried out by Cytochrome P450 2B4 (CYP450) immobilization into a polypyrrole matrix onto the gold working electrode. Chronoamperometric experiments show a PB diffusion coefficient of 2.42x10(-6)cm(2)s(-1), a reproducibility and repeatability in terms of residual standard deviation (RSD) of 13% and 5.51%, respectively, and a limit of detection (LOD) of 0.289 micromol dm(-3) (alpha=beta=0.05) for the developed CYP450-biosensor chip. Its performance has been showed by the determination of PB in pharmaceutical drugs. HPLC has been used as reference technique.


Effectiveness of Ultrasound-Guided Versus Anatomic Landmark-Guided Corticosteroid Injection on Pain, Physical Function, and Safety in Patients With Subacromial Impingement Syndrome: A Systematic Review and Meta-analysis.
The aim of the study was to compare the efficacy and safety of ultrasound-guided versus anatomic landmark-guided corticosteroid injection for the treatment of subacromial impingement syndrome. PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Scopus, ClinicalTrials.gov , CBM, CNKI, and Wanfang databases were searched from inception to August 15, 2021, for randomized controlled trials comparing ultrasound-guided versus anatomic landmark-guided injections of corticosteroids for the treatment of subacromial impingement syndrome. Twelve randomized controlled trials with 891 patients were included in this study; 454 patients received ultrasound-guided injections and 437 received anatomic landmark-guided injections. Pooled results showed that ultrasound-guided injection was more beneficial for pain relief (10 trials; mean difference = -0.58; 95% confidence interval = -1.05 to -0.10; P = 0.017) and functional improvement (11 trials; standard mean difference = -0.84; 95% confidence interval = -1.41 to -0.27; P = 0.004). There was no significant difference in shoulder range of motion. In the subgroup analysis, there was a significant difference in pain relief and functional improvement at 6-8 wks and with methylprednisolone. Ultrasound-guided injection of corticosteroids is potentially superior to anatomic landmark-guided injection in improving the clinical symptoms of subacromial impingement syndrome; however, these findings should be interpreted with some caution as the quality of evidence was rated as moderate to very low.


Molecular basis of tyrosinase-negative oculocutaneous albinism. A single base mutation in the tyrosinase gene causing arginine to glutamine substitution at position 59.
Tyrosinase-negative oculocutaneous albinism (OCA) is one of classical inborn errors of metabolism, characterized by a complete lack of melanin pigments in the eyes and skin. We have isolated and characterized the tyrosinase gene of one child (F. S.) affected with tyrosinase-negative OCA. Sequence analysis reveals a single-base mutation in the exon 1 (a G to A transition at nucleotide residue 312), causing the Arg (CGG) to Gln (CAG) substitution at position 59. This base change eliminates one MspI site and creates a new BstNI site in the patient's exon 1, which is invaluable for screening other OCA patients and heterozygote carriers for this mutation. We are thus able to confirm that the patient F. S. is homozygous for this OCA allele. The family members of the patient F. S. are phenotypically normal, but are shown to be heterozygote carriers. Transfection of the mutant gene fails to give rise to detectable tyrosinase activity in transient expression assays, suggesting that the mutation affects the stability or the catalytic activity of the enzyme. We therefore propose that the albino phenotype of the patient F. S. is a consequence of the Arg to Gln substitution at position 59 caused by a point mutation in the tyrosinase gene.


Surgical treatment for lung metastasis of inflammatory myofibroblastic tumor of the lung: A case report.
Inflammatory myofibroblastic tumor (IMT) is a rare disease that is considered an intermediate neoplasm, with the risk of recurrence and metastasis. Surgical treatment is the standard therapy for IMT, although there are only a few reports of surgery for lung metastasis of pulmonary IMT. We opine that surgical treatment might be effective not only for localized tumors, but also for cases of lung metastasis of IMT.


Stem cell-derived neuronal relay strategies and functional electrical stimulation for treatment of spinal cord injury.
The inability of adult mammals to recover function lost after severe spinal cord injury (SCI) has been known for millennia and is mainly attributed to a failure of brain-derived nerve fiber regeneration across the lesion. Potential approaches to re-establishing locomotor function rely on neuronal relays to reconnect the segregated neural networks of the spinal cord. Intense research over the past 30 years has focused on endogenous and exogenous neuronal relays, but progress has been slow and the results often controversial. Treatments with stem cell-derived neuronal relays alone or together with functional electrical stimulation offer the possibility of improved repair of neuronal networks. In this review, we focus on approaches to recovery of motor function in paralyzed patients after severe SCI based on novel therapies such as implantation of stem cell-derived neuronal relays and functional electrical stimulation. Recent research progress offers hope that SCI patients will one day be able to recover motor function and sensory perception.


Role of the renal sympathetic nerve in renal glucose metabolism during the development of type 2 diabetes in rats.
Recent clinical studies have shown that renal sympathetic denervation (RDX) improves glucose metabolism in patients with resistant hypertension. We aimed to elucidate the potential contribution of the renal sympathetic nervous system to glucose metabolism during the development of type 2 diabetes. Uninephrectomised diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats underwent RDX at 25 weeks of age and were followed up to 46 weeks of age. RDX decreased plasma and renal tissue noradrenaline (norepinephrine) levels and BP. RDX also improved glucose metabolism and insulin sensitivity, which was associated with increased in vivo glucose uptake by peripheral tissues. Furthermore, RDX suppressed overexpression of sodium-glucose cotransporter 2 (Sglt2 [also known as Slc5a2]) in renal tissues, which was followed by an augmentation of glycosuria in type 2 diabetic OLETF rats. Similar improvements in glucose metabolism after RDX were observed in young OLETF rats at the prediabetic stage (21 weeks of age) without changing BP. Here, we propose the new concept of a connection between renal glucose metabolism and the renal sympathetic nervous system during the development of type 2 diabetes. Our data demonstrate that RDX exerts beneficial effects on glucose metabolism by an increase in tissue glucose uptake and glycosuria induced by Sglt2 suppression. These data have provided a new insight not only into the treatment of hypertensive type 2 diabetic patients, but also the pathophysiology of insulin resistance manifested by sympathetic hyperactivity.


Cortical gamma oscillations: the functional key is activation, not cognition.
Cortical oscillatory synchrony in the gamma range has been attracting increasing attention in cognitive neuroscience ever since being proposed as a solution to the so-called binding problem. This growing literature is critically reviewed in both its basic neuroscience and cognitive aspects. A physiological "default assumption" regarding these oscillations is introduced, according to which they signal a state of physiological activation of cortical tissue, and the associated need to balance excitation with inhibition in particular. As such these oscillations would belong among a variety of generic neural control operations that enable neural tissue to perform its systems level functions, without implementing those functions themselves. Regional control of cerebral blood flow provides an analogy in this regard, and gamma oscillations are tightly correlated with this even more elementary control operation. As correlates of neural activation they will also covary with cognitive activity, and this typically suffices to account for the covariation between gamma activity and cognitive task variables. A number of specific cases of gamma synchrony are examined in this light, including the original impetus for attributing cognitive significance to gamma activity, namely the experiments interpreted as evidence for "binding by synchrony". This examination finds no compelling reasons to assign functional roles to oscillatory synchrony in the gamma range beyond its generic functions at the level of infrastructural neural control.


Promiscuous phosphoketolase and metabolic rewiring enables novel non-oxidative glycolysis in yeast for high-yield production of acetyl-CoA derived products.
Carbon-conserving pathways have the potential of increasing product yields in biotechnological processes. The aim of this project was to investigate the functionality of a novel carbon-conserving pathway that produces 3 mol of acetyl-CoA from fructose-6-phosphate without carbon loss in the yeast Saccharomyces cerevisiae. This cyclic pathway relies on a generalist phosphoketolase (Xfspk), which can convert xylulose-5-phosphate, fructose-6-phosphate and sedoheptulose-7-phosphate (S7P) to acetyl phosphate. This cycle is proposed to overcome bottlenecks from the previously reported non-oxidative glycolysis (NOG) cycle. Here, in silico simulations showed accumulation of S7P in the NOG cycle, which was resolved by blocking the non-oxidative pentose phosphate pathway and introducing Xfspk and part of the riboneogenesis pathway. To implement this, a transketolase and transaldolase deficient S. cerevisiae was generated and a cyclic pathway, the Glycolysis AlTernative High Carbon Yield Cycle (GATHCYC), was enabled through xfspk expression and sedoheptulose bisphosphatase (SHB17) overexpression. Flux through the GATHCYC was demonstrated in vitro with a phosphoketolase assay on crude cell free extracts, and in vivo by constructing a strain that was dependent on a functional pathway to survive. Finally, we showed that introducing the GATHCYC as a carbon-conserving route for 3-hydroxypropionic acid (3-HP) production resulted in a 109% increase in 3-HP titers when the glucose was exhausted compared to the phosphoketolase route only.


N400 amplitude, latency, and variability reflect temporal integration of beat gesture and pitch accent during language processing.
This study examines how across-trial (average) and trial-by-trial (variability in) amplitude and latency of the N400 event-related potential (ERP) reflect temporal integration of pitch accent and beat gesture. Thirty native English speakers viewed videos of a talker producing sentences with beat gesture co-occurring with a pitch accented focus word (synchronous), beat gesture co-occurring with the onset of a subsequent non-focused word (asynchronous), or the absence of beat gesture (no beat). Across trials, increased amplitude and earlier latency were observed when beat gesture was temporally asynchronous with pitch accenting than when it was temporally synchronous with pitch accenting or absent. Moreover, temporal asynchrony of beat gesture relative to pitch accent increased trial-by-trial variability of N400 amplitude and latency and influenced the relationship between across-trial and trial-by-trial N400 latency. These results indicate that across-trial and trial-by-trial amplitude and latency of the N400 ERP reflect temporal integration of beat gesture and pitch accent during language comprehension, supporting extension of the integrated systems hypothesis of gesture-speech processing and neural noise theories to focus processing in typical adult populations.


Schizophrenia, abnormal connection, and brain evolution.
Abnormalities of functional connection between specialized areas in the human brain may underlie the symptoms which constitute the schizophrenia syndrome. Callosal and intrahemispheric fibres may be equally involved. The clinical emergence of symptoms in the later stages of brain maturation may be dependent on myelination of these fibre groups, both of which have extended myelination cycles. Ontogenetically earlier variants of the same mechanism could theoretically result in dyslexia and the syndromes of Kanner and Gilles de la Tourette. As new and unique extensions of specialized function emerge within the evolving brain, biological trial and error of connection both within and between them may produce individuals possessing phylogenetically advanced abilities, or equally, others possessing a wide range of abnormalities including those which comprise the schizophrenia syndrome. A dormant phenotypic potential for schizophrenia may exist in individuals who never develop symptoms during the course of a lifetime though some of these may become clinically apparent under the influence of various precipitating factors. It is concluded that abnormal functional connection and its normal and "supernormal" counterparts may be natural, essential, and inevitable consequences of brain evolution, and that this may have been so throughout the history of vertebrate brain evolution.


AKT2 identified as a potential target of mir-29a-3p via microRNA profiling of patients with high proliferation lacrimal gland adenoid cystic carcinoma.
The lacrimal gland adenoid cystic carcinoma (LACC) is a major orbital malignancy. The recurrence rate and mortality rate are higher in high proliferation LACC(HP-LACC) compared with low proliferation LACC(LP-LACC). In this study, miRNA microarray was used to explore the differentially expressed miRNAs profiling between HP-LACC and LP-LACC and its potential signaling pathway. Tissues from 17 patients with LACC were collected and made into tissue microarrays. Patients were divided into a high proliferation group and a low proliferation group based on Ki-67 value. HE, immunofluorescence (IF), and Immunohistochemistry (IHC) were performed on the tissue microarrays. Eight LACC tissues(4 HP-LACC and 4 LP-LACC) were made into miRNA microarrays and analyzed for miRNA profiles. Differentially expressed miRNAs were analyzed by volcano plot and heat map. Target gene were predicted using the miRWalk and miRDB for these differentially expressed miRNAs, the intersection of the results are used as targets for further gene ontology and KEGG pathway analysis.The four differentially expressed miRNAs were validated by qRT-PCR, the miRNAs with statistically significant differences validated by dual luciferase reporter and qRT-PCR. Finally, IHC was used for their downstream signaling pathway proteins.HE staining showed the presence of tubular, cribriform, and basaloid structures in LACC. IF showed the presence of CK7,P63 fluorescence expression in all three structures.Patients were divided into HP-LACC and LP-LACC based on Ki-67 median value of 11%. IHC and survival analysis showed with the increase of KI-67 ratio, the proportion of P63 decreased, and the expression of P53 increased. The disease-free survival and overall survival of the patients decreased. IHC and survival analysis showed as Ki-67 expression increased, P63 expression decreased, P53 expression elevated, with prognosis worse. Heat map and volcano plot yielded 15 differentially expressed miRNAs between HP-LACC and LP-LACC.The 15 differential miRNAs were used to predict target genes in miRWalk and miRDB databases respectively, and there were 559 target genes after intersection.559 predicted target genes obtained. Go and KEGG analysis showed that these target genes exerted important biological functions through multiple signaling pathways. Among the 15 differentially expressed miRNAs, miR-29a-3p was verified to be significant by qRT-PCR. Dual luciferase reporter and tissue microarray immunohistochemical assays validated that AKT2 was a direct target gene of miR-29a-3p. Current studies have identified differentially expressed miRNAs associated with LACCs of variable proliferation ability, and found that AKT2 is a direct target gene of miR-29a-3p, which will contribute to target gene therapy in patients with high proliferation LACC in the future.


[Clinical Characteristics and Prognostic Factors of Patients with Primary Parotid Gland Lymphoma].
To explore the clinical characteristics and prognostic factors of patients with primary parotid gland lymphoma, and construct a prognostic model nomogram for patients with primary diffuse large B-cell lymphoma (DLBCL) of parotid gland. Primary parotid gland lymphoma and primary DLBCL of parotid gland patients from 1984 to 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analysis were conducted to determine the independent prognostic factors of primary parotid gland lymphoma and primary DLBCL of parotid gland, respectively. According to the established independent prognostic factors of primary DLBCL of parotid gland, nomogram was built to predict 3- and 5-year survival, and the discrimination and calibration of the model were evaluated by concordance index (C-index) and calibration plots. A total of 2 610 patients with primary parotid gland lymphoma were identified. Their median age was 66(15-99) years old, the male to female ratio was 1∶1.8, and 20.5% of them was primary DLBCL of parotid gland, which was the most common histological subtype in aggressive lymphomas. Multivariate Cox regression analysis showed that sex, age, Ann Arbor stage, years of diagnosis, marital status, histological subtype, surgery, and radiation were the independent prognostic factors of primary parotid gland lymphoma, while age, marital status, surgery, and chemotherapy were the independent prognostic factors of primary DLBCL of parotid gland. The C-index of the prediction model was 0.702(95%CI: 0.696-0.768), reflecting a good discrimination ability. The predicted value probability of the calibration plots was close to the actual value probability, reflecting a good accuracy ability. Sex, age, Ann Arbor stage, years of diagnosis, marital status, histological subtype, surgery, and radiation were the independent prognostic factors of primary parotid gland lymphoma. The nomogram survival prediction model for primary DLBCL of parotid gland patients can assist clinical decision effectively.


Expression and prognostic value of the aldehyde dehydrogenase 1 (ALDH1) and N-myc downstream regulated gene 2 (NDRG2) as potential markers in human astrocytomas.
In this study, immunohistochemical analysis was used to evaluate the expression of ALDH1 and NDRG2 in astrocytoma tissue samples and normal brain tissues. ALDH1 protein staining displayed that AlDH1 expression was not detectable in eight astrocytoma tissues (8/36) and in all of normal brain tissues. There was a significant difference between ALDH1 expression and WHO grades (P = 0.03). Furthermore, no correlation was determined between expression levels of ALDH1 and other clinicopathological characteristics including age, sex, and tumor size. Immunohistochemistry showed that a high level of NDRG2 protein expression was markedly detected in normal brain tissues and expression of NDRG2 protein was significantly decreased in astrocytoma tissues. There was a significant association between pathological grading and NDRG2 expression level (P < 0.001, Table 1), but no correlation was determined between expression levels of NDRG2 and other clinicopathological characteristics including age, sex, and tumor size. We also obtained detailed follow-up data and evaluated the association of ALDH1/NDRG2 expressions with overall survival. Kaplan-Meier survival and log-rank analysis indicated that the patients with high proportion of ALDH1-positive cells and low proportion of NDRG2-positive had shorter overall survival (P < 0.001; P = 0.001). Univariate analysis indicated that the high proportion of ALDH1-positive cells (P < 0.001), the low proportion of NDRG2-positive cells (P = 0.009), and the advanced grade (P < 0.005) were markedly linked to the prognosis in patients. Furthermore, in the multivariate analysis, ALDH1 cells' expression (P = 0.012), low proportion of NDRG2-positive cells (P = 0.025), and advanced grade (P < 0.03) were linked to poor overall survival. Our results suggest that NDRG2 expression is related to decreased survival rates and NDRG2 may be a potential marker in the astrocytoma prognosis. NDRG2 may be a potential marker in the astrocytoma prognosis. ALDH1 expression was related to advanced pathological grade and survival rate in astrocytoma patients.


Efficient manufacturing of therapeutic mesenchymal stromal cells with the use of the Quantum Cell Expansion System.
The use of bone marrow-derived mesenchymal stromal cells (MSCs) as a cellular therapy for various diseases, such as graft-versus-host disease, diabetes, ischemic cardiomyopathy and Crohn's disease, has produced promising results in early-phase clinical trials. However, for widespread application and use in later phase studies, manufacture of these cells must be cost-effective, safe and reproducible. Current methods of manufacturing in flasks or cell factories are labor-intensive, involve a large number of open procedures and require prolonged culture times. We evaluated the Quantum Cell Expansion System for the expansion of large numbers of MSCs from unprocessed bone marrow in a functionally closed system and compared the results with a flask-based method currently in clinical trials. After only two passages, we were able to expand a mean of 6.6 × 10(8) MSCs from 25 mL of bone marrow reproducibly. The mean expansion time was 21 days, and cells obtained were able to differentiate into all three lineages: chondrocytes, osteoblasts and adipocytes. The Quantum was able to generate the target cell number of 2.0 × 10(8) cells in an average of 9 fewer days and in half the number of passages required during flask-based expansion. We estimated that the Quantum would involve 133 open procedures versus 54,400 in flasks when manufacturing for a clinical trial. Quantum-expanded MSCs infused into an ischemic stroke rat model were therapeutically active. The Quantum is a novel method of generating high numbers of MSCs in less time and at lower passages when compared with flasks. In the Quantum, the risk of contamination is substantially reduced because of the substantial decrease in open procedures.


Endoscopic treatment of sagittal suture synostosis - a critical analysis of current management strategies.
While many centers nowadays offer minimally invasive techniques for the treatment of single suture synostosis, surgical techniques and patient management vary significantly. We provide an overview of how scaphocephaly treated with endoscopic techniques is managed in the reported series and analyze the crucial steps that need to be dealt with during the management process. We performed a review of the published literature including all articles that examined sagittal-suture synostosis treated with endoscopic techniques as part of single- or multicenter studies. Fourteen studies reporting results of 885 patients were included. We identified 5 key steps in the management of patients. A total of 188 patients were female and 537 male (sex was only specified in 10 articles, for 725 included patients, respectively). Median age at surgery was between 2.6 and 3.9 months with a total range from 1.5 to 7.0 months. Preoperative diagnostics included clinical and ophthalmologic examinations as well as neuropsychological and genetic consultations if needed. In 5 publications, a CT scan was routinely performed. Several groups used anthropometric measurements, mostly the cephalic index. All groups analyzed equally recommended to perform endoscopically assisted craniosynostosis surgery with postoperative helmet therapy in children < 3 months of age, at least for non-syndromic cases. There exist significant variations in surgical techniques and patient management for children treated endoscopically for single suture sagittal synostosis. This heterogeneity constitutes a major problem in terms of comparability between different strategies.


Retracted: Cell Fate and Tissue Remodeling in Canine Urethral Repair Using a Bone Marrow Mesenchymal Stem Cell+Endothelial Progenitor Cell Amniotic Patch.
The Editors of Tissue Engineering: Part A retract the article entitled, "Cell Fate and Tissue Remodeling in Canine Urethral Repair Using a Bone Marrow Mesenchymal Stem Cell+Endothelial Progenitor Cell Amniotic Patch," by Wenxin Zhang, Xin Zhang, Yihua Zhang, Xinke Zhang, Tong Zou, Wen Zhao, Yangou Lv, Jinglu Wang, Pengxiu Dai, Hao Cui, Yi Zhang, Dengke Gao, Chenmei Ruan, and Xia Zhang (epub ahead of print September 21, 2020; DOI: http://doi.org/10.1089/ten.tea.2020.0129). After the online publication of the article, the authors have indicated that they "feel that we have not yet studied our work completely and some new great results are discovered. So after carefully thinking, we are going to rearrange this manuscript and try to give more precise model. [sic]" The authors have not explained what those expected results will be, so it remains unclear the direction their work is headed. The authors also indicated that they plan to submit an updated version of the paper to Tissue Engineering in the future. Upon submission the new manuscript will undergo rigorous peer review, and there is no guarantee of acceptance.


Enhancement of microbiome management by machine learning for biological wastewater treatment.
Here, we propose to develop microbiome-based machine learning models to predict the response of biological wastewater treatment systems to environmental or operational disturbances or to design specific microbiomes to achieve a desired system function. These machine learning models can be used to enhance the stability of microbiome-based biological systems and warn against the failure of these systems.


Pertussis prevalence among adult patients with acute cough.
Bordetella pertussis infection remains an important health problem in adults due to the increasing prevalence in recent years. Pertussis in adults can be easily overlooked or misdiagnosed. We aimed to determine the prevalence of pertussis in adult patients with acute cough and the clinical features of the pertussis cases. Internal Medicine and Pulmonology inpatient wards and outpatient clinics were screened between March 2017 and June 2018. Patients with cough duration between 1 week and 1 month were enrolled. Those who were on antibiotics for more than 5 days were excluded. A total of 115 patients were enrolled. Nasopharyngeal swabs were taken and real-time polymerase chain reaction analyses were done. According to the pertussis case definition, 47.8% of the patients were diagnosed with probable pertussis. We found the prevalence of pertussis as 3.5% in our cohort. All of the patients with pertussis had a history of paroxysmal cough with a mean duration of 20 days. These results show that pertussis continues to be a health problem for adults and may present with acute cough. The growing number of adult pertussis cases suggest that vaccination of children is inadequate to prevent pertussis and the concept of 'lifelong vaccination' should be strengthened.


Progonostic effect of GSTM1/GSTT1 polymorphism in determining cardiovascular diseases risk among type 2 diabetes patients in South Indian population.
Cardiovascular disease (CVD) is a significant complication of type 2 diabetes mellitus (T2DM), with oxidative stress playing a significant role. Glutathione S-transferase (GST) polymorphisms - GSTM1, GSTT1 - have been linked to CVD and T2DM. The role of GSTM1 and GSTT1 in CVD development among T2DM patients in the South Indian population is investigated in this study. The volunteers were grouped as Group 1: control, Group 2: T2DM, Group 3: CVD, and Group 4: T2DM with CVD (n = 100 each). Blood glucose, lipid profile, plasma GST, MDA, and total antioxidants were measured. GSTM1 and GSTT1 were genotyped using PCR. GSTT1 plays a significant role in the development of T2DM and CVD [OR 2.96(1.64-5.33), < 0.001 and 3.05(1.67-5.58), < 0.001] while GSTM1 null genotype was not associated with disease development. Individuals with dual null GSTM1/GSTT1 genotype had the highest risk of developing CVD [3.70(1.50-9.11), 0.004]. Group 2 and 3 individuals showed higher lipid peroxidation and lower total antioxidant levels. Pathway analysis further indicated that GSTT1 significantly affects GST plasma levels. GSTT1 null genotype may be considered a contributing factor that increases the susceptibility and risk of CVD and T2DM in the South Indian population.


Simultaneous en bloc endotracheal tube insertion with GlideScope® Titanium™ video laryngoscope use: a randomized-controlled trial.
Intubation-associated trauma with the GlideScope is rare, but when it occurs, it is likely due to advancing the endotracheal tube (ETT) blindly between the direct view of the oropharynx and the video view of the glottis. It is also occasionally difficult to advance the ETT to the glottic aperture despite a good view of the glottis on the monitor. One technique to potentially address both issues is to introduce the ETT en bloc with the GlideScope, thus visualizing the ETT tip throughout its entire path. We hypothesized that this en bloc technique could be faster and potentially easier than the standard technique. Fifty patients with normal-appearing airways who required orotracheal intubation for elective surgery were randomly allocated to intubation with either the en bloc or the standard (GlideScope-first-then-ETT) technique. A three-dimensional printed clip was utilized to secure the ETT to the GlideScope during en bloc insertion. The primary outcome was time to intubation, defined from mask removal to first end-tidal carbon dioxide detection, recorded by a blinded observer. Secondary outcomes were subjective ease of intubation (100-mm visual analogue scale [VAS], 0 = easy; 100 = difficult), number of intubation attempts/failures, and incidence of oropharyngeal trauma (bleeding). The median [interquartile range (IQR)] intubation time was 36 [31-42] sec with the en bloc technique vs 41 [37-50] sec with the standard technique (difference in medians, 5 sec; 95% confidence interval [CI], 2 to 11; P = 0.008). The median [IQR] ease of intubation VAS was 11 [9-21] mm with the en bloc technique, and 15 [11-24] mm with the standard technique (difference in medians, 4 mm; 95% CI, -2 to 8; P = 0.19). Laryngoscopic grade and number of intubation attempts were similar between the groups; there was no oropharyngeal trauma noted. In this study of video laryngoscopy, intubation was slightly faster with the en bloc technique than with the standard GlideScope intubation technique, although the clinical importance of this difference is unknown. www.clinicaltrials.gov (NCT02787629); registered 1 June 2016.


Toward newborn screening of metachromatic leukodystrophy: results from analysis of over 27,000 newborn dried blood spots.
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulfatase A (ARSA), which results in the accumulation of sulfatides. Newborn screening for MLD may be considered in the future as innovative treatments are advancing. We carried out a research study to assess the feasibility of screening MLD using dried blood spots (DBS) from de-identified newborns. To minimize the false-positive rate, a two-tier screening algorithm was designed. The primary test was to quantify C16:0-sulfatide in DBS by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The screening cutoff was established based on the results from 15 MLD newborns to achieve 100% sensitivity. The secondary test was to measure the ARSA activity in DBS from newborns with abnormal C16:0-sulfatide levels. Only newborns that displayed both abnormal C16:0-sulfatide abundance and ARSA activity were considered screen positives. A total of 27,335 newborns were screened using this two-tier algorithm, and 2 high-risk cases were identified. ARSA gene sequencing identified these two high-risk subjects to be a MLD-affected patient and a heterozygote. Our study demonstrates that newborn screening for MLD is highly feasible in a real-world scenario with near 100% assay specificity.


The crashed voice--a potential for change: a psychotherapeutic view.
Jungian analysis is based on the work and extensive writings of C.G. Jung. Jung worked for a while with Freud who expected him to carry on the work of psychoanalysis. However, the two men were very different and Jung broke away from the Freudian model to develop his own unique view of the unconscious and to explore what he believed to be its innate capacity for healing. He said: "My life is the story of the self realization of the unconscious. Everything in the unconscious seeks outward manifestation, and the personality too desires to evolve out of its unconscious conditions and to experience itself as a whole." (Memories, Dreams, Reflections C.G. Jung. 1963) The goal of the therapeutic work for Jung was individuation--the never ending process of becoming fully oneself. This process represents the individual's capacity to choose creatively between both internal and external necessity without denying either. Jungian analysts work in some similar ways to other analysts and see dreams as central to this process. They also sometimes work with archetypal symbols and other forms of creative expression such as painting or dance. All the methods used are there to enable patients to explore their unconscious, understand and accept who they are, and access powers for healing the self. People in creative and expressive fields are often drawn to the work because of its belief in the uniqueness of the individual and its understanding of the healing power of a creative relationship to oneself.


Labor analgesia for the parturient with cardiac disease: what does an obstetrician need to know?
Maternal heart disease complicates 0.2-3% of pregnancies. The optimal management of the pregnant patient with cardiac disease depends on the cooperative efforts of the obstetrician, the cardiologist and the anesthesiologist involved in peripartum care. A comprehensive understanding of physiology of pregnancy and pathophysiology of underlying cardiac disease is of primary importance in provision of obstetric analgesia or anesthesia for this high-risk group of patients. This article will review the current guidelines and standards pertinent to management of obstetric analgesia and anesthesia in parturients with cardiac disease.


Vasodilator therapy after heart transplantation: effects of inhaled nitric oxide and intravenous prostacyclin, prostaglandin E1, and sodium nitroprusside.
Vasodilator therapy is frequently needed to treat pulmonary hypertension after heart transplantation. In the present study, the effects of intravenous sodium nitroprusside, prostacyclin, prostaglandin E1, and inhaled nitric oxide (5, 10, and 20 parts per million) on central hemodynamics, right ventricular function, and pulmonary selectivity were evaluated shortly after heart transplantation. Hemodynamic measurements were made after surgery in the intensive care unit. The intravenous vasodilators were compared at equipotent infusion rates. Effects of inhaled nitric oxide were measured after 10 minutes inhalation at each dose level. Cardiac output, stroke volume, right ventricular end-diastolic volume, and central filling pressures were highest with prostacyclin (16 +/- 2 ng/kg/min) compared with both prostaglandin E1 (202 +/- 27 ng/kg/min) and sodium nitroprusside (1.0 +/- 0.2 microgram/kg/min). Systemic and pulmonary vascular resistance were lowest with prostacyclin. None of the intravenous vasodilators induced a selective pulmonary vasodilation. In contrast, nitric oxide inhalation induced a selective decrease in pulmonary vascular resistance, with no change in systemic vascular resistance. Cardiac output increased with nitric oxide, whereas mean pulmonary arterial pressure, transpulmonary pressure gradient, and central venous pressure decreased, with the most pronounced effect at an inhaled concentration of 20 parts per million. Prostacyclin is the best choice for intravenous vasodilator therapy after heart transplantation. However, inhaled nitric oxide is the only selective pulmonary vasodilator, which should be used in cases of pulmonary hypertension and severe right ventricular failure associated with systemic hypotension.


NIN-like protein transcription factors regulate leghemoglobin genes in legume nodules.
Leghemoglobins enable the endosymbiotic fixation of molecular nitrogen (N2) in legume nodules by channeling O2 for bacterial respiration while maintaining a micro-oxic environment to protect O2-sensitive nitrogenase. We found that the NIN-like protein (NLP) transcription factors NLP2 and NIN directly activate the expression of leghemoglobins through a promoter motif, resembling a "double" version of the nitrate-responsive elements (NREs) targeted by other NLPs, that has conserved orientation and position across legumes. CRISPR knockout of the NRE-like element resulted in strongly decreased expression of the associated leghemoglobin. Our findings indicate that the origins of the NLP-leghemoglobin module for O2 buffering in nodules can be traced to an ancient pairing of NLPs with nonsymbiotic hemoglobins that function in hypoxia.


The adenine-modified edible chitosan films containing choline chloride and citric acid mixture.
A series of biopolymeric chitosan-based (Ch) films were prepared with choline chloride and citric acid plasticizer (deep eutectic solvent, DES). An effect of adenine (A, vitamin B4) addition on the functional properties of these films was evaluated. Several physicochemical and mechanical properties were tested: Fourier-transformed infrared spectra proved DES's plasticizing and crosslinking effect, while scanning electron microscopy and atomic force microscopy techniques confirmed the possible phase separation after adenine addition. These changes affected the mechanical characteristics and the water vapor and oxygen permeability. The prepared materials are not water soluble because the CA acts as a crosslinker. The adenine addition on antioxidative and antimicrobial properties was also checked. It was found that Ch-DES materials with A exhibit improved antioxidative properties (55.8-66.1% of H2O2 scavenging activity) in contrast to the pristine chitosan-DES material (51.1% of H2O2 scavenging activity), while the material is still non-mutagenic (lack of growth of Salmonella typhimurium) and possesses antimicrobial features (no E. coli observed for all the tested films and inhibition zones noted for S. aureus). The mentioned properties, reduced oxygen transmission (1.6-2.1 g m-2 h-1), and mechanical characteristics within the range of typical food packaging plastics proved the potential of Ch-DES-A films in the packaging sector. Moreover, the antioxidative properties, usage of substrates being allowed as food additives, and the presence of adenine create the advantage of the Ch-DES-A materials as edible coatings, being also a source of Vitamin B4.


High-resolution two-dimensional gel analysis of proteins in wing imaginal discs: a data base of Drosophila.
An improved method of high-resolution two-dimensional gel electrophoresis has been used to study the patterns of protein synthesis in wing imaginal discs of late instar larvae of Drosophila melanogaster. A small number of discs were radiolabeled with a mixture of 14C-labeled amino acids or with [35S]methionine and the pattern of labeled proteins was analyzed. One thousand and twenty-five polypeptides (787 acidic (IEF) and 238 basic (NEPHGE] from wing discs of several wild-type strains have so far been separated and cataloged. All these polypeptides have been numbered and presented in a reference map for further studies. When comparing patterns of label we have found small quantitative differences in rate of synthesis between individuals of the same strain, not due to sexual differences, and very few quantitative and qualitative differences between groups of individuals of different strains.


Negative antibody response to long-term treatment of facial spasm with botulinum toxin.
Over a period of 163 weeks, 223 injections of botulinum A toxin were administered to 38 patients with facial spasm syndromes. The maximum cumulative toxin dose was 553 units, the maximum number of injections in any given patient was 16, and the maximum dosage of any given injection was 52.5 units. Sera from these patients showed no antibody production when measured with a standard mouse lethality bioassay.


Intersecting Barriers to PrEP Awareness and Uptake in Black Men Who Have Sex with Men in Atlanta, GA: a Syndemic Perspective.
Pre-exposure prophylaxis (PrEP) can sharply reduce HIV transmission risk, yet has not been widely adopted among those at highest risk for HIV, including Black men who have sex with men (BMSM). To better understand the evolving landscape of PrEP uptake in this at-risk population, we sought to examine psychosocial factors associated with PrEP uptake in a sample of BMSM residing in the Atlanta, GA, area. BMSM were recruited through online social media, LGBT venues, and participant referral, and self-reported demographic and psychosocial information via computer-assisted self-interview. Multivariate logistic regression was used to examine psychosocial factors associated with PrEP uptake. In 293 BMSM, most (N = 260; 88.7%) reported awareness of PrEP yet few (N = 30; 10.1%) reported ever having taken PrEP. BMSM reporting more syndemic conditions were less likely to be current PrEP users (OR = 0.59; 95% CI: 0.36, 0.96). BMSM reporting recent condomless anal sex (CAS) with a partner met online (adjusted odds ratio (aOR) = 2.53; 95% CI: 1.07, 5.93), or who reported having chlamydia (aOR = 8.21; 95% CI: 1.42, 47.67) or STI-related symptoms (aOR = 4.35; 95% CI: 1.32, 14.37) in the past 3 months, or genital warts in their lifetime (aOR = 7.74; 95% CI: 2.47, 24.21) were more likely to have ever used PrEP. Sexual orientation stigma from health care providers was negatively associated with PrEP uptake (OR = 0.81, 95% CI: 0.68, 0.95) among BMSM reporting recent CAS and multiple partners. Syndemic and stigma theories may inform strategies for improving PrEP uptake in BMSM.


Management of heart failure patients in Poland.
Over the next 10 years, heart failure is likely to become a medical and sociological problem as a result of improved treatment of ischaemic heart disease and hypertension. At present, in Poland, there are only 50% of the cardiological or cardiac surgery procedures (coronarography, PTCA, CABG, surgery of congenital or acquired heart disease) performed compared to Western Europe. After being registered on the waiting list, it can take anything between 3 and 12 months before the procedure is done. Patients with heart failure have diagnostic tests such as ECG, chest X-ray, and biochemical evaluation performed regardless of the level of care. When echocardiography, exercise testing or Holter monitoring is required, it is done at specialist or reference specialist facilities with a waiting time of approximately 1-3 months. Pharmaceutical treatment of CHF is also inadequate. ACE inhibitors are prescribed in approximately 68% of patients. The average prescribed dosage is far from that recommended in guidelines. Only 18-29% of patients with HF are on beta blockers. The improvement of cardiological care standards depends mainly on the financial resources of State Health System Agencies.


Implementation of the Water Framework Directive: Lessons Learned and Future Perspectives for an Ecologically Meaningful Classification Based on Phytoplankton of the Status of Greek Lakes, Mediterranean Region.
The enactment of the Water Framework Directive (WFD) initiated scientific efforts to develop reliable methods for comparing prevailing lake conditions against reference (or nonimpaired) states, using the state of a set biological elements. Drawing a distinction between impaired and natural conditions can be a challenging exercise. Another important aspect is to ensure that water quality assessment is comparable among the different Member States. In this context, the present paper offers a constructive critique of the practices followed during the WFD implementation in Greece by pinpointing methodological weaknesses and knowledge gaps that undermine our ability to classify the ecological quality of Greek lakes. One of the pillars of WDF is a valid lake typology that sets ecological standards transcending geographic regions and national boundaries. The national typology of Greek lakes has failed to take into account essential components. WFD compliance assessments based on the descriptions of phytoplankton communities are oversimplified and as such should be revisited. Exclusion of most chroococcal species from the analysis of cyanobacteria biovolume in Greek lakes/reservoirs and most reservoirs in Spain, Portugal, and Cyprus is not consistent with the distribution of those taxa in lakes. Similarly, the total biovolume reference values and the indices used in classification schemes reflect misunderstandings of WFD core principles. This hampers the comparability of ecological status across Europe and leads to quality standards that are too relaxed to provide an efficient target for the protection of Greek/transboundary lakes such as the ancient Lake Megali Prespa.


The selective cyclooxygenase-2 inhibitor parecoxib markedly improves the ability of the duodenum to regulate luminal hypertonicity in anaesthetized rats.
To examine whether the prevention of post-operative duodenal ileus by treatment with parecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, affects the ability of the duodenum to respond to luminal hypertonicity. The proximal duodenums of anaesthetized rats were perfused with hypertonic NaCl solutions with osmolalities of 400, 500, 600 or 700 mOsm kg(-1) , and the effects on mucosal permeability, motility, transepithelial net fluid flux and effluent osmolality were assessed in the absence (control) and presence of parecoxib. Parecoxib-treated, but not control animals, exhibited duodenal contractions, which were reduced by the nicotinic receptor antagonists mecamylamine and hexamethonium and by perfusion with 700 mOsm kg(-1) . All animals responded to luminal hypertonicity with induction of net fluid secretion, which peaked at an osmolality of 500 mOsm kg(-1) . The hypertonicity-induced increases in fluid secretion were twofold greater in parecoxib-treated than in control rats and attenuated by nicotinic receptor blockade. The decrease in luminal osmolality correlated with the osmolality of the perfusion solution in both control and parecoxib-treated animals but the osmolality-adjusting capability was markedly better in the latter group. Rats exposed to duodenal luminal distension responded to hypertonicity with a greater fluid secretion and a larger decrease in luminal osmolality than control rats. Perfusion with 700 mOsm kg(-1) increased mucosal permeability in parecoxib-treated animals only, an effect abolished by nicotinic receptor blockade. Parecoxib markedly improved the ability of the duodenum to sense and to decrease luminal hypertonicity by a mechanism most probably involving inhibition of COX-2 and stimulation of nicotinic acetylcholine receptors.


The protective action of R56865 against ouabain-induced intoxication in rat heart isolated atria and ventricles.
The action of R56865 has been examined on the contractile effects produced by ouabain concentrations interacting with high (3 microM) and low (300 microM) affinity digitalis receptors on electrically stimulated ventricular strips isolated from rat. R56865 1 microM reduced the increase in resting tension produced by ouabain 300 microM and left unalterated the inotropic effect evoked by ouabain 3 and 300 microM that was reduced by higher concentrations (3 and 6 microM) of R56865. The action of R56865 was also studied on ouabain-induced intoxication in electrically stimulated and spontaneously beating atria of rat. On electrically stimulated (3 Hz) whole atria, R56865 0.3 microM reduced the maximal increase in resting tension produced by ouabain 300 microM and delayed the time to onset of the ouabain-induced arrhythmias but did not affect ouabain's inotropic effect. Higher concentrations of R56865 were required to reduce the inotropic effect of ouabain. The protective action of R56865 against ouabain-induced intoxication was most pronounced on spontaneously beating atria where it reduced spontaneous rate of beats. Experiments in electrically driven left atria indicated that only a part of the protective effect of R56865 could be related to its bradycardic action. The effect of R56865 was also examined on ouabain-induced inhibition of sodium pump in human red blood cells. R56865 6 microM did not modify the inhibition produced by ouabain (from 0.3 to 10 nM), this indicates that the protective action of R56865 against ouabain-induced intoxication is not due to an interaction with the inhibitory effect of ouabain on sodium pump.


Comparison of the diagnostic efficacy of white light endoscopy and magnifying endoscopy with narrow band imaging for early gastric cancer: a meta-analysis.
Magnifying endoscopy with narrow band imaging (ME-NBI) is widely used in gastroscopy, especially in the diagnosis of early gastric cancer. The purpose of this meta-analysis is to compare the diagnostic efficacy of white light imaging (WLI) and that of ME-NBI for early gastric cancer. PubMed/MEDLINE, EMBASE, and the Cochrane Library were searched to identify studies which met the inclusion criteria. A random-effects model was used to calculate overall sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) to assess the diagnostic efficacy of WLI and ME-NBI in early gastric cancer. Sensitivity analysis was performed to assess the stability of the results. Ten studies met the inclusion criteria, and included 1724 patients and 2153 lesions. The pooled sensitivity, specificity, and AUC for the diagnosis of early gastric cancer using WLI were 0.48 [95 % confidence interval (CI) 0.39-0.57; I (2) = 78.6 %], 0.67 (95 % CI 0.62-0.71; I (2) = 81.9 %), and 0.62, respectively. The pooled sensitivity, specificity, and AUC using ME-NBI were 0.83 (95 % CI 0.79-0.87; I (2) = 79.8 %), 0.96 (95 % CI 0.95-0.97; I (2) = 89.3 %), and 0.96, respectively. The studies showed a high degree of heterogeneity. Further sensitivity analysis was mainly performed for the studies of small lesions (mean size 10 mm or less) and the studies with a the score of 12 points or greater in the literature quality assessment, and the AUCs for ME-NBI for diagnosis of early gastric cancer were between 0.93 and 0.98, which suggested that the diagnostic value was still high and stable. Compared with WLI, ME-NBI can effectively diagnose early gastric cancer.


Preferential use of plant glycans for growth by Bacteroides ovatus.
B. ovatus is a member of the human gut microbiota with a broad capability to degrade complex glycans. Here we show that B. ovatus degrades plant polysaccharides in a preferential order, and that glycan structural complexity plays a role in determining the prioritisation of polysaccharide usage.


Oxidative stress in pathogenesis of chronic obstructive pulmonary disease: cellular and molecular mechanisms.
Chronic obstructive pulmonary disease (COPD) is a slowly progressive condition characterized by airflow limitation, which is largely irreversible. Oxidative stress and inflammation are the major hallmarks of COPD. Reactive oxygen species, either directly or via the formation of lipid peroxidation products, such as 4-hydroxy-2-nonenal and F2-isoprostanes, may play a role in enhancing the inflammation through the activation and phosphorylation of mitogen-activated protein kinases (MAPKs) and redox-sensitive transcription factors such as nuclear factor-kappaB and activator protein-1 in COPD. In addition, activation of the MAPK family leads to the transactivation of transcription factors and coactivators (chromatin remodeling). This eventually results in expression of genes regulating a battery of distinct proinflammatory, antioxidant, and stress response genes. The presence of an oxidative stress has important consequences on several events of lung physiology and for the pathogenesis of COPD. These include increased sequestration of neutrophils in the pulmonary microvasculature, oxidative inactivation of antiproteases and surfactants, hypersecretion of mucus, membrane lipid peroxidation, mitochondrial respiration, alveolar epithelial injury/permeability, breakdown/remodeling of extracellular matrix, and apoptosis. Oxidative stress may have a role in the poor efficacy of corticosteroids in COPD. This review discusses cellular and molecular changes that occur in response to smoking and oxidative stress in the pathogenesis of COPD.


Artificial confocal microscopy for deep label-free imaging.
Widefield microscopy of optically thick specimens typically features reduced contrast due to "spatial crosstalk", in which the signal at each point in the field of view is the result of a superposition from neighbouring points that are simultaneously illuminated. In 1955, Marvin Minsky proposed confocal microscopy as a solution to this problem. Today, laser scanning confocal fluorescence microscopy is broadly used due to its high depth resolution and sensitivity, but comes at the price of photobleaching, chemical, and photo-toxicity. Here, we present artificial confocal microscopy (ACM) to achieve confocal-level depth sectioning, sensitivity, and chemical specificity, on unlabeled specimens, nondestructively. We equipped a commercial laser scanning confocal instrument with a quantitative phase imaging module, which provides optical path-length maps of the specimen in the same field of view as the fluorescence channel. Using pairs of phase and fluorescence images, we trained a convolution neural network to translate the former into the latter. The training to infer a new tag is very practical as the input and ground truth data are intrinsically registered, and the data acquisition is automated. The ACM images present significantly stronger depth sectioning than the input (phase) images, enabling us to recover confocal-like tomographic volumes of microspheres, hippocampal neurons in culture, and 3D liver cancer spheroids. By training on nucleus-specific tags, ACM allows for segmenting individual nuclei within dense spheroids for both cell counting and volume measurements. In summary, ACM can provide quantitative, dynamic data, nondestructively from thick samples, while chemical specificity is recovered computationally.


On-line monitoring of methanol in n-hexane by an organic-phase alcohol biosensor.
An organic-phase alcohol biosensor has been developed by co-entrapping alcohol oxidase and horseradish peroxidase within an ionotropy polymer hydrogel matrix fabricated from silica gel particles, hydroxyethyl carboxymethylcellulose, an adduct of 3-methoxy-4-ethoxybenzaldehyde and 4-tert-butylpyridinium acetohydrazone, and octadecylsilica particles. The viability of the immobilised enzymes for the biocatalytic reaction of methanol in n-hexane was comparatively studied by using a bulk cell or a volume-changeable flow-through cell coupled with an oxygen optical transducer. It was found that the microenvironment around the enzyme, the deterioration property of the enzyme, the substrate throughput and the mass transfer process of the reactant in the bioreactor were the crucial parameters affecting the performance of the alcohol organic-phase biosensor. Our optimal biosensor was constructed from a flow-through cell packed with small particles of immobilised enzymes and it could maintain the biocatalytic reaction at high and stable rate for on-line detection of methanol in n-hexane under flow operation mode. The biosensor had an analytical working range of 2.3-90 mM methanol in n-hexane. The response times (t95) were 4.5 and 7.5 min for 60 and 10 mM methanol, respectively. The operational lifetime of the biosensor was more than 45 assays and the shelf lifetime was longer than 2 weeks. The biosensor has been successfully applied to determine the methanol content in a commercial gasoline-methanol blend sample with good recovery.


[Social egg freezing: which problems?].
In today's society, many women push pregnancy further away from the "right" childbearing age. Assisted reproduction, except egg donation, is unable to fully overcome the effect of age on fertility loss. The effectiveness of oocyte vitrification is demonstrated, and oocyte vitrification is allowed in the French Bioethics law of 2011. In the French law, oocyte' s cryopreservation is proposed to oocyte donors without child. Social egg freezing for non-medical reason is already legal in some countries, but leads to new debates and discussions.


Pharmaceutical wastewater being composite mixture of environmental pollutants may be associated with mutagenicity and genotoxicity.
Pharmaceutical industries are amongst the foremost contributor to industrial waste. Ecological well-being is endangered owing to its facile discharge. In the present study, heavy metals and organic contaminants in waste water were characterized using atomic absorption spectrophotometer and GC-MS, respectively. Mutagenicity and genotoxic potential of pharmaceutical waste water were investigated through bacterial reverse mutation assay and in vitro comet assay, respectively. Ames test and comet assay of first sample were carried out at concentrations of 100, 50, 25, 12.5, 6.25 % v/v effluent with distilled water. Chromium (Cr), lead (Pb), arsenic (As), and cadmium (Cd) were found in high concentrations as compared to WHO- and EPA-recommended maximum limits. Arsenic was found to be the most abundant metal and its maximum concentration was 0.8 mg.L(-1). GC-MS revealed the presence of lignocaine, digitoxin, trimethoprim, caffeine, and vitamin E in waste water. Dose-dependent decrease in mutagenic index was observed in both strains. Substantial increase in mutagenicity was observed for TA-100, when assay was done by incorporating an enzyme activation system, whereas a slight increase was detected for TA-102. In vitro comet assay of waste water exhibited decrease in damage index and percentage fragmentation with the increase in dilution of waste water. Tail length also decreased with an increase in the dilution factor of waste water. These findings suggest that pharmaceutical waste water being a mix of different heavy metals and organic contaminants may have a potent mutagenic and genotoxic effect on exposed living organisms.