Comparative activity of Sant7 and anti-IL-6, IL-6R monoclonal antibodies in a murine model of B-cell lymphoma.
Interleukin-6 (IL-6) plays a central role in the pathogenesis of several autoimmune and inflammatory diseases as well as B-cell lymphoproliferative disorders. This work describes the effects of the recombinant or adenovirally-delivered IL-6 superantagonist Sant7, anti-IL-6 and IL-6 receptor monoclonal antibodies in a severe murine model of human B-cell lymphoma induced in SCID mice by transplantation of an LCL-41 cell line variant (isotype-switched IgM>IgG). Survival of 60% of the animals treated with anti-gp130 was observed up to day 33, while about 20% of the animals survived with anti-gp80 and Sant7 treatment. No survival was observed with the anti-IL-6 monoclonal antibody treatment. No significant change in serum and peritoneal levels of human IL-6 (hIL-6) and soluble human IL-6 receptor (shIL-6R) was observed in the recombinant Sant7-treated group towards the control group. The anti-gp80 monoclonal antibody induced significant increase of both hIL-6R and hIL-6 in serum and peritoneum. The anti-gp130 monoclonal antibody treatment determined a reduction of the seric shIL-6R and a significant increase of the seric hIL-6. Anti-IL-6 monoclonal antibody administration resulted in a reduction of serum and in an increase of peritoneal hIL-6. Treatment with adenoviral Sant7 was associated with a reduction of circulating shIL-6R, hIgG and mSAP. However, only marginal anti-tumor efficacy of the adenoviral Sant7 was observed. Overall, the present data suggest a potential for anti-hIL-6 therapy in B-cell lymphomas. Less severe animal models might be useful to better evaluate Sant7 efficacy alone or in combination with other anti-IL-6 therapeutics.


Serefeddin Sabuncuoğlu (1385-1468) on pediatric skull fractures. Historical vignette.
Serefeddin Sabuncuoğlu (1385-1468) presents medieval management of pediatric skull fractures in his textbook Cerrahiyyetu'l Haniyye (Imperial Surgery). He was a Turkish surgeon who lived in the Ottoman Empire during the 15th century. Cerrahiyyetu'l Haniyye, the first example of surgical textbook in the Turkish medical literature, was beautifully illustrated with his own drawings. In this historical article, the sections of Cerrahiyyetu'l Haniyye pertinent to surgical techniques and instruments for pediatric head injury are critically reviewed.


Structural investigation of a polysaccharide (Fr. I) isolated from the aqueous extract of an edible mushroom, Volvariella diplasia.
A water-soluble polysaccharide, (Fr. I) isolated from the aqueous extract of an edible mushroom, Volvariella diplasia, is composed of D-glucose, D-mannose, and D-galactose in a molar ratio 3:1:1. Compositional analysis, methylation analysis, periodate oxidation study, Smith degradation, and NMR studies (1H, 13C, DQF-COSY, TOCSY, NOESY, ROESY, HMQC, and HMBC) revealed the presence of the following repeating unit in the polysaccharide: [Formula: see text].


Population biomonitoring of micronutrient intakes in children using urinary spot samples.
Urinary spot samples are a promising method for the biomonitoring of micronutrient intake in children. Our aim was to assess whether urinary spot samples could be used to estimate the 24-h urinary excretion of potassium, phosphate, and iodine at the population level. A cross-sectional study of 101 children between 6 and 16 years of age was conducted. Each child collected a 24-h urine collection and three urinary spot samples (evening, overnight, and morning). Several equations were used to estimate 24-h excretion based on the urinary concentrations of each micronutrient in the three spot samples. Various equations and spot combinations were compared using several statistics and plots. Ninety-four children were included in the analysis (mean age: 10.5 years). The mean measured 24-h urinary excretions of potassium, phosphate, and iodine were 1.76 g, 0.61 g, and 95 µg, respectively. For potassium, the best 24-h estimates were obtained with the Mage equation and morning spot (mean bias: 0.2 g, correlation: 0.27, precision: 56%, and misclassification: 10%). For phosphate, the best 24-h estimates were obtained with the Mage equation and overnight spot (mean bias: - 0.03 g, correlation: 0.54, precision: 72%, and misclassification: 10%). For iodine, the best 24-h estimates were obtained with the Remer equation and overnight spot (mean bias: - 8 µg, correlation: 0.58, precision: 86%, misclassification: 16%). Urinary spot samples could be a good alternative to 24-h urine collection for the population biomonitoring of iodine and phosphate intakes in children. For potassium, spot samples were less reliable.


Immunochemical characterization of gastrinlike and cholecystokininlike peptides released in dogs in response to a peptone meal.
This study was designed to examine and compare the nature of gastrinlike and cholecystokininlike peptides released into the portal and peripheral venous circulation in response to a peptone meal. Six dogs were prepared with portal venous catheters and gastric fistulas. Portal and peripheral venous sera were obtained before and after gastric infusion of a 10% peptone meal. Serum levels of gastrin and cholecystokinin immunoreactive peptides were determined by radioimmunoassay using two distinct peptide region-specific antibody preparations. These separate antibody preparations demonstrated specificity for (a) C-terminal tetradecapeptide gastrin (4-17hG17), heptadecapeptide gastrin (G17), and big gastrin (G34) (gastrin antibody); and (b) all biologically active forms of gastrin and cholecystokinin (gastrin-cholecystokinin antibody). Using the antibody preparation with specificity for gastrin and not cholecystokinin, the mean basal immunoreactive gastrin from portal (8.33 +/- 2.4 fmol/ml, mean +/- SEM) and from peripheral (6.19 +/- 0.9 fmol/ml) venous sera both increased after peptone infusion, with an early peak (2 min in portal and 4 min in peripheral serum) and a second peak at 30 min in both circulations. Measurements using antibodies with specificity for both cholecystokinin and gastrin yielded strikingly different results. The portal venous serum peptide concentration (49 +/- 10 fmol/ml) increased sharply within 30 s after peptone infusion to a single peak at 2 min (139 +/- 37 fmol/ml). The basal peripheral venous serum peptide concentration (43 +/- 8.8 fmol/ml) increased more gradually to a single peak at 8 min (78 +/- 14 fmol/ml). Studies with Sephadex (G-50 superfine) gel chromatography indicated that gastrin released in response to the peptone meal was primarily G17. However, of the peptides released in response to the peptone meal that were recognized by the gastrin-cholecystokinin antibody, greater than 80% were shown to be distinct from gastrin. Gel chromatographic studies demonstrated that peptone meal-stimulated immunoreactive cholecystokinin release consisted of two major peaks, eluting in positions identical to those of intact cholecystokinin (CCK33) and the octapeptide of cholecystokinin (CCK8).


Natalizumab discontinuation is associated with a rebound of cognitive impairment in multiple sclerosis patients.
Natalizumab discontinuation is associated with a disease reactivation in multiple sclerosis (MS) patients. Whether this reactivation involves also cognitive functions is not known to date. To assess the persistence of the effect of natalizumab on cognitive functions 1 year after its discontinuation, we compared the longitudinal changes of cognitive performances in two groups of patients. The interrupters, 30 MS patients, have stopped natalizumab due to PML concern, and the continuers, 28 MS patients, continued the treatment. The cognitive impairment index (CII) was used as main outcome measure. As expected, during the natalizumab treatment, we observed a significant reduction of the relapse rate and the number of gadolinium-enhancing lesions along with a reduction of the CII. After 1 year of discontinuation, the beneficial effect on cognitive functions was lost in the interrupters group, as the mean CII increased in comparison with the mean at the end of natalizumab treatment (12.2 ± 7.9 vs 9.3 ± 8.1, p < 0.0001). As opposite, in the continuers group, the CII further decreased after an additional year of treatment (8.4 ± 5.1 vs 9.8 ± 4.6, p = 0.007). A multivariate logistic regression model revealed as predictors of cognitive worsening male sex, disease duration, and the treatment discontinuation. The worsening of cognitive functions after natalizumab discontinuation goes in parallel with the clinical/radiological disease reactivation. Our data reinforce the hypothesis that, in the short-term, natalizumab exerts its positive impact on cognitive functions by means of its anti-inflammatory properties.


Adapting automated instrumentation for high-throughput calcium isotope measurements by multi-collector inductively coupled plasma mass spectrometry.
Large, efficiently generated datasets of calcium isotope ratios offer tremendous utility in an increasing number of scientific disciplines. Modern analytical capabilities in mass spectrometry present unique challenges to previously established sample preparation techniques, the extent of which must be thoroughly examined before these data are interpreted and reported. This study addresses key methodological challenges in the determination of calcium isotopes using state-of-the-art, commercially available instruments. Automated ion chromatography was used to isolate calcium from carbonate- and seawater-like samples prior to analysis by multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS). A new, membrane-bearing desolvator (Apex-Ω) is implemented and achieves enhanced sensitivity, yet necessitates an update to established sample preparation techniques due to previously unobserved matrix effects. Performance of this method was assessed through analyses of multiple standard reference materials (SRM 915b, USGS EN-1, and seawater) and several in-house standards using a Neptune MC-ICP-MS instrument. The enhanced sensitivity afforded by the Apex-Ω also yields pronounced matrix effects during mass spectrometry, resulting specifically from heightened sample Na and Sr content and deviations in sample [Ca] from their bracketing standards. While the latter can be addressed by a concentration correction, the first two matrix effects are mitigated using a modified chromatography technique that implements unique rinsing protocols. This precise (0.14‰ 2σ), high-throughput method is very reproducible for small sample amounts and, at optimal efficiency, can generate approximately 140 sample δ44/40 Ca values per week with 5 h of in-person effort per day. Documented matrix effects are successfully mitigated through corrections and modified chromatographic techniques. Additionally, this method may be permuted to accommodate most major cations.


HMGB3 modulates ROS production via activating TLR cascade in Apostichopus japonicus.
High mobility group box protein 3 (HMGB3) regulates proliferation and inflammatory response in vertebrates. However, its functional roles in invertebrates are largely unknown. In this study, a HMGB3 homologue molecule was identified from Apostichopus japonicus (designated as AjHMGB3) by RACE approach. The full-length cDNA of AjHMGB3 was of 2298 bp with an open reading frame of 1320 bp encoding a 439-amino-acid (aa) residue protein. Structural analysis then conducted and the results revealed that AjHMGB3 processed two conserved HMGBs (133-204 and 210-279 aa) and an acidic tail. The results of subsequent multiple sequence alignment and phylogenetic analysis both indicated that AjHMGB3 belongs to a new member of HMGB3 protein subfamily. Furthermore, AjHMGB3 was expressed in all examined tissues except in tentacles and particularly highly expressed in the intestine, as indicated by spatial expression analysis results. The Vibrio splendidus challenge in vivo and lipolysaccharide (LPS) stimulation in vitro can significantly upregulate the mRNA expression of AjHMGB3 in coelomocytes. This finding is consistent with the expression profiles of TLR cascade members. We further investigated the expression profiles of AjMyD88 and Ajp105 after the gain- or loss-of-function of AjHMGB3 in coelomocytes. The results showed that AjMyD88 and Ajp105 were upregulated 2.19- and 2.83-fold in AjHMGB3 overexpressed treatment and downregulated 0.38- and 0.43-fold in the AjHMGB3 silencing group. The p50 subunit displayed expression profiles that are identical to those of AjMyD88 and Ajp105 according to the Western blot results. In the same condition, the respiratory burst was increased by 37.5% in the AjHMGB3 overexpressed group and depressed by 28.2% in the AjHMGB3 knock-down group. Our present findings collectively suggested that AjHMGB3 acted as an NF-κB activator and produced ROS production in sea cucumbers.


Qualitative and quantitative detection of DNA amplified with HRP-modified SiO2 nanoparticles using scanning electrochemical microscopy.
Qualitative and quantitative detection of DNA was achieved by a "sandwich" DNA sensor through SG/TC (substrate generation and tip collection) mode of scanning electrochemical microscopy (SECM). The "sandwich" DNA structure was formed by the hybridization of thiol-tethered oligodeoxynucleotide probes (capture probe), assembled on the gold substrate surface, with target DNA and biotinylated indicator probe. HRP (horseradish peroxidase)-wrapped SiO2 nanoparticles were linked to the sandwich structure through biotin-streptavidin interaction. Hydroquinone (H2Q) was oxidized to benzoquinone (BQ) at the modified substrate surface where sequence-specific hybridization had occurred through the HRP-catalyzed reaction in the presence of H2O2. The detection was based on the reduction of BQ generated on the modified substrate by SECM tip. For SECM imaging experiment, we structured the microsensor platform through localized desorption of 1-dodecanethiol monolayer. Approach curves were employed for quantitative detection of DNA concentration. The detection limit of complementary DNA was as low as 0.8pM. This technique is promising for the application on electrochemical DNA chip.


Complications and mortality patterns due to Plasmodium falciparum malaria in hospitalized adults and children, Rourkela, Orissa, India.
Of 1857 Plasmodium falciparum malaria patients hospitalized from 1995 to 1998, 608 had severe malaria and 83 died. Acute renal failure, jaundice and respiratory distress were common in adults whereas children frequently had severe anaemia. Cerebral malaria occurred equally in adults and children but recovery from coma was quicker in children. Multiple complications caused high mortality in adults.


A new comparison of marine dispersion model performances for Fukushima Dai-ichi releases in the frame of IAEA MODARIA program.
A detailed intercomparison of marine dispersion models applied to the releases from Fukushima Dai-ichi nuclear power plant was carried out in the frame of MODARIA program, of the IAEA. Models were compared in such a way that the reasons of the discrepancies between them can be assessed (i.e., if they are due to the hydrodynamic part, the dispersion part, and the ultimate reasons). A sequential chain of dispersion exercises was carried out with this purpose. The overall idea is to harmonize models, making them run with the same forcing in a step-by-step procedure, in such a way that the main agent in producing discrepancy between models can be found. It was found that the main reason of discrepancies between models is due to the description of the hydrodynamics. However, once this has been suppressed, some variability between model outputs remains due to intrinsic differences between models (as numerical schemes). The numerical experiments were carried out for a perfectly conservative radionuclide and for (137)Cs (including water/sediment interactions). Model outputs for this radionuclide were also compared with measurements in water and sediments.


HIV-related and Epstein-Barr virus-associated anal Burkitt's lymphoma: report of a case.
This article describes and discusses primary Burkitt's lymphoma of the anus which is an extremely rare site of origin. A 38-year-old HIV+ Rwandan farmer had an 8-cm x 13-cm anal tumor. Histopathology and immunohistology provided evidence of an Epstein-Barr virus-associated Burkitt's lymphoma. Chemotherapy in combination of virostatic therapy is the gold standard for treatment, but because of economic constraints surgical treatment was the only practicable intervention and an abdominoperineal resection of the anorectum was performed. Because of the AIDS epidemic and the increase of anal malignant pathologies, anal Burkitt's lymphoma may appear more frequently. Adequate treatment is available for only a small percentage of patients.


Characterization and the potential immune role of class A scavenger receptor member 4 (SCARA4) in bacterial infection in turbot (Scophthalmus maximus L.).
The class A scavenger receptors play important roles in innate immunity and are distributed on plasma membrane of macrophages and other cell types. Notably, the class A scavenger receptor 4 (SCARA4) contains a typical C-type (calcium-dependent) lectin domain, which belongs to the collectin family of pattern recognition receptors and is involved in the immune response against infection. Here, one turbot SCARA4 gene was identified with a 2,292 bp open reading frame (ORF) encoding 763 amino acid residues. Multiple sequence analysis and phylogenetic analysis confirmed that SmSCARA4 gene was more close to that of P. olivaceus. Gene structure and syntenic analysis showed conserved exon/intron organization pattern and syntenic pattern across selected vertebrate species. Tissue distribution analysis showed SmSCARA4 was expressed in all the tested healthy tissues with the relative high expression levels in skin, gill and spleen. Following both E. tarda and V. anguillarum challenge in vivo, SmSCARA4 was significantly repressed in gill and intestine. Remarkably, SmSCARA4 showed the strongest binding ability to LPS and strongest upregulation in turbot head kidney macrophages in response to LPS. Knockdown and overexpression of SmSCARA4 revealed its interactions with the two pro-inflammatory cytokines, TNF-α and IL-1β. Finally, repression of SmSCARA4 via combined treatment of LPS and overexpression of SmSCARA4 construct in turbot head kidney macrophages further indicated an inhibitory role of SmSCARA4 in LPS-stimulated inflammation. Taken together, turbot SmSCARA4 plays an important role in turbot immunity, especially in the mucosa-related systems; SmSCARA4 possesses strong binding specificity to LPS, and exerts protective roles in response to LPS infection by reducing the release of pro-inflammatory cytokines. The mechanisms of inhibitory role of SmSCARA4 in LPS-elicited inflammation await further investigation.


Loss of Ras GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) inhibits the progression of ovarian cancer in coordination with ubiquitin-specific protease 10 (USP10).
Ovarian cancer (OC) is one of the most lethal gynecological malignancies. However, the molecular mechanisms underlying the development of OC remain unclear. Here, we report that loss of Ras GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) inhibits the progression of OC cells. Analysis of databases and clinical specimens showed that G3BP1 is upregulated in OC. The Kaplan-Meier plot results showed that G3BP1 is highly expressed in OC with a poor clinical outcome. Moreover, loss-of-G3BP1 suppresses the proliferation, migration, and invasion of OC cells. Protein-protein interaction network analysis and immunoprecipitation assay showed that ubiquitin-specific protease 10 (USP10) interacts with G3BP1. We next found that USP10 coordinately promotes tumor progression with G3BP1. Moreover, loss of USP10could restore the G3BP1-induced proliferation, migration, and invasion of OC cells. These data indicate that G3BP1 coordinated with USP10 to facilitate the progression of OC cells, and that G3BP1 may become a treatment target for OC.


Implementation of a physician assistant/hospitalist service in an academic medical center: impact on efficiency and patient outcomes.
Accreditation Council on Graduate Medical Education (ACGME) duty hour restrictions have led to the widespread implementation of non-house staff services in academic medical centers, yet little is known about the quality and efficiency of patient care on such services. To evaluate the quality and efficiency of patient care on a physician assistant/hospitalist service compared with that of traditional house staff services. Retrospective cohort study. Inpatient general medicine service of a 747-bed academic medical center. A total of 5194 consecutive patients admitted to the general medical service from July 2005 to June 2006, including 992 patients on the physician assistant/hospitalist service and 4202 patients on a traditional house staff service. A geographically localized service staffed with physician assistants and supervised by hospitalists. Length of stay (LOS), cost of care, inpatient mortality, intensive care unit (ICU) transfers, readmissions, and patient satisfaction. Patients admitted to the study service were younger, had lower comorbidity scores, and were more likely to be admitted at night. After adjustment for these and other factors, and for clustering by attending physician, total cost of care was marginally lower on the study service (adjusted costs 3.9% lower; 95% confidence interval [CI] -7.5% to -0.3%), but LOS was not significantly different (adjusted LOS 5.0% higher; 95% CI, -0.4% to +10%) as compared with house staff services. No difference was seen in inpatient mortality, ICU transfers, readmissions, or patient satisfaction. For general medicine inpatients admitted to an academic medical center, a service staffed by hospitalists and physician assistants can provide a safe alternative to house staff services, with comparable efficiency.


The Selective Peroxisome Proliferator-Activated Receptor Gamma Modulator CHS-131 Improves Liver Histopathology and Metabolism in a Mouse Model of Obesity and Nonalcoholic Steatohepatitis.
CHS-131 is a selective peroxisome proliferator-activated receptor gamma modulator with antidiabetic effects and less fluid retention and weight gain compared to thiazolidinediones in phase II clinical trials. We investigated the effects of CHS-131 on metabolic parameters and liver histopathology in a diet-induced obese (DIO) and biopsy-confirmed mouse model of nonalcoholic steatohepatitis (NASH). Male C57BL/6JRj mice were fed the amylin liver NASH diet (40% fat with trans-fat, 20% fructose, and 2% cholesterol). After 36 weeks, only animals with biopsy-confirmed steatosis and fibrosis were included and stratified into treatment groups (n = 12-13) to receive for the next 12 weeks (1) low-dose CHS-131 (10 mg/kg), (2) high-dose CHS-131 (30 mg/kg), or (3) vehicle. Metabolic parameters, liver pathology, metabolomics/lipidomics, markers of liver function and liver, and subcutaneous and visceral adipose tissue gene expression profiles were assessed. CHS-131 did not affect body weight, fat mass, lean mass, water mass, or food intake in DIO-NASH mice with fibrosis. CHS-131 improved fasting insulin levels and insulin sensitivity as assessed by the intraperitoneal insulin tolerance test. CHS-131 improved total plasma cholesterol, triglycerides, alanine aminotransferase, and aspartate aminotransferase and increased plasma adiponectin levels. CHS-131 (high dose) improved liver histology and markers of hepatic fibrosis. DIO-NASH mice treated with CHS-131 demonstrated a hepatic shift to diacylglycerols and triacylglycerols with a lower number of carbons, increased expression of genes stimulating fatty acid oxidation and browning, and decreased expression of genes promoting fatty acid synthesis, triglyceride synthesis, and inflammation in adipose tissue. Conclusion: CHS-131 improves liver histology in a DIO and biopsy-confirmed mouse model of NASH by altering the hepatic lipidome, reducing insulin resistance, and improving lipid metabolism and inflammation in adipose tissue.


[Diphtheria toxin titration using "Staphylococcus aureus" protein A (author's transl)].
The antigen-antibody reaction between diphtheria toxin and its corresponding IgG antibody may be visualized if IgG are adsorbed on the surface of S. aureus cells carrying protein A (SpA). If enough antigen is mixed with SpA--IgG, a visible agglutination occurs. On a glass slide, a rapid test can detect 0.3 Lf/ml toxin. If the mixtures are incubated overnight at 37 degrees C, the highest dilution of toxin producing agglutination is 0.01 to 0.02 Lf/ml for a given batch of toxin. The sensitivities of this or of the biological titration using the lethal effect on guinea-pigs are the same. The high sensitivity of the skin reaction was however not approached.


Macrophages induce antibody-dependent cytostasis but not lysis in guinea pig leukaemic cells.
Guinea pig and mouse peritoneal macrophages formed antibody-dependent rosettes with guinea pig L2C leukaemic cells, but were unable either to phagocytose the cells or to kill them extracellularly as judged by the retention of 51Cr. Macrophages previously activated by BCG in vivo also failed to exhibit phagocytosis or cytoxicity towards the antibody-coated cells. These failures could not be attributed to deficient function of the macrophages nor to antigenic modulation of the L2C cells. The antibodies involved were capable of mediating lysis by complement, and ADCC by human leukocytes. However macrophages were cytostatic to antibody-coated L2C cells in that uptake of 3H-thymidine or 3H-deoxycytidine was abruptly and in some cases completely inhibited upon cell contact being established. Antigenic modulation which had proceeded sufficiently to protect against lysis by complement did not protect against cytostasis. Syngeneic macrophages had greater cytostatic activity than did allogeneic or xenogeneic. Macrophage activation by BCG did not result in significantly increased cytostasis. A univalent antibody derivative Fab/c was also capable of mediating cytostatis by the macrophages.


Implication of the Drosophila beta-amyloid peptide binding-like protein AMX in Notch signaling during early neurogenesis.
Lateral inhibition provides a mechanism to regulate neuroblast specification during early neurogenesis in Drososphila melanogaster embryos. This mechanism is mediated by the highly conserved Notch pathway. Defective lateral inhibition results in CNS hyperplasia at the expense of ectoderm development, hence genes causing this defect are called neurogenic. D. melanogaster almondex (amx) is a maternal neurogenic gene, crucially required for embryonic lateral inhibition. Genetic interaction studies previously revealed amx as a positive Notch pathway partner in several processes, acting potentially upstream of Notch. We show here that embryonic overexpression of Notch intracellular domain partially rescues maternal lack of amx, suggesting a role for AMX at the level of Notch processing. Our molecular data reveal that amx is ubiquitously expressed and encodes a conserved putative transmembrane protein, composed of several domains that are differently required for amx function in the fly. Sequence comparisons identify AMX as a Drosophila Beta-amyloid peptide Binding Protein (BBP) family member, a BBP-like protein or dBLP. Based on these data, we discuss the potential molecular function of AMX in early neurogenesis.


Energetic costs and implications of the intake of plant secondary metabolites on digestive and renal morphology in two austral passerines.
Seed-eating birds have a diet of high nutritional value; however, they must cope with plant secondary metabolites (PSM). We postulated that the detoxification capacity of birds is associated with a metabolic cost, given that the organs responsible for detoxification significantly contribute to energetic metabolism. We used an experimental approach to assess the effects of phenol-enriched diets on two passerines with different feeding habits: the omnivorous rufous-collared sparrow (Zonotrichia capensis) and the granivorous common diuca-finch (Diuca diuca). The birds were fed with one of three diets: control diet, supplemented with tannic acid, or supplemented with Opuntia ficus-indica phenolic extract (a common food of the sparrow but not the finch). After 5 weeks of exposure to the diets, we measured basal metabolic rates (BMR), energy intake, glucuronic acid output and digestive and kidney structure. In both species, detoxification capacity expressed as glucuronic acid output was higher in individuals consuming phenol-enriched diets compared to the control diet. However, whereas sparrows increase energy intake and intestinal mass when feeding on phenol-enriched diets, finches had lower intestinal mass and energy intake remains stable. Furthermore, sparrows had higher BMR on phenol-enriched diets compared to the control group, whereas in the finches BMR remains unchanged. Interspecific differences in response to phenols intake may be determined by the dietary habits of these species. While both species can feed on moderate phenolic diets for 5 weeks, energy costs may differ due to different responses in food intake and organ structure to counteract the effects of PSM intake.


Opsonization of malaria-infected erythrocytes activates the inflammasome and enhances inflammatory cytokine secretion by human macrophages.
Antibody opsonization of Plasmodium falciparum-infected erythrocytes (IE) plays a crucial role in anti-malarial immunity by promoting clearance of blood-stage infection by monocytes and macrophages. The effects of phagocytosis of opsonized IE on macrophage pro-inflammatory cytokine responses are poorly understood. Phagocytic clearance, cytokine response and intracellular signalling were measured using IFN-γ-primed human monocyte-derived macrophages (MDM) incubated with opsonized and unopsonized trophozoite-stage CS2 IE, a chondroitin sulphate-binding malaria strain. Cytokine secretion was measured by bead array or ELISA, mRNA using quantitative PCR, and activation of NF-κB by Western blot and electrophoretic mobility shift assay. Data were analysed using the Mann-Whitney U test or the Wilcoxon signed rank test as appropriate. Unopsonized CS2 IE were not phagocytosed whereas IE opsonized with pooled patient immune serum (PPS) were (Phagocytic index (PI)=18.4, [SE 0.38] n=3). Unopsonized and opsonized IE induced expression of TNF, IL-1β and IL-6 mRNA by MDM and activated NF-κB to a similar extent. Unopsonized IE induced secretion of IL-6 (median= 622 pg/ml [IQR=1,250-240], n=9) but no IL-1β or TNF, whereas PPS-opsonized IE induced secretion of IL-1β (18.6 pg/mL [34.2-14.4]) and TNF (113 pg/ml [421-17.0]) and increased IL-6 secretion (2,195 pg/ml [4,658-1,095]). Opsonized, but not unopsonized, CS2 IE activated caspase-1 cleavage and enzymatic activity in MDM showing that Fc receptor-mediated phagocytosis activates the inflammasome. MDM attached to IgG-coated surfaces however secreted IL-1β in response to unopsonized IE, suggesting that internalization of IE is not absolutely required to activate the inflammasome and stimulate IL-1β secretion. It is concluded that IL-6 secretion from MDM in response to CS2 IE does not require phagocytosis, whereas secretion of TNF and IL-1β is dependent on Fcγ receptor-mediated phagocytosis; for IL-1β, this occurs by activation of the inflammasome. The data presented in this paper show that generating antibody responses to blood-stage malaria parasites is potentially beneficial both in reducing parasitaemia via Fcγ receptor-dependent macrophage phagocytosis and in generating a robust pro-inflammatory response.


Control of rotation angles of multilayer graphene on SiC (0001‾) by substrate off-direction and angle.
Graphene on SiC (0001‾) tends to grow in multiple layers and does not have a single orientation relation with the SiC substrate. It has been considered impossible to control the rotation angle of multilayer graphene on SiC (0001‾). In this study, we grew graphene on off-axis SiC substrates with various off angles from 0° to 8° and investigated their in-plane rotation and electronic structures systematically. As the off angle toward the [112‾0]SiCdirection increased, graphene rotated by 30° with respect to SiC became less dominant and instead, graphene rotated by 30 ± 2.5° appeared. We also found that the uniformity of the graphene rotation angle was relatively high on SiC substrates with a small off angle toward the [11‾00]SiCdirection. Our results suggest that the step-terrace structure defined by the substrate off-direction and angle plays an important role in the controllability of the rotation angle of graphene.


Specific serum antibody responses in channel catfish (Ictalurus punctatus) provide limited protection against Streptococcus ictaluri challenge.
Passive immunization studies were conducted to determine the role of specific antibodies in immunity to Streptococcus ictaluri. Adult channel catfish (Ictalurus punctatus) were injected i.p. with tryptic soy broth as control or with 1.5 × 10(7)colony-forming units (cfu) S. ictaluri/fish at 0, 30, and 60 d, and serum was collected 90 d after the original challenge. Fish were passively immunized by i.p. injection with serum from the tryptic soy broth (TSB) control group, anti-S. ictaluri serum from fish immunized three times and sampled at 90 d (SSI), or heat-inactivated anti-S. ictaluri serum from fish immunized three times and sampled at 90 d (HISSI). These passively immunized fish were then challenged 72 h later with 1.5 × 10(8)cfu S. ictaluri/fish. Over 21 d, the mean cumulative percent survival was 43.3 (TSB), 63.3 (SSI), and 50.0 (HISSI). A significant difference in cumulative percent survival was noted between the TSB and the HISSI groups, and significant differences were noted between these groups and the SSI group. Serum obtained from immunized fish 72 h after passive immunization exhibited increased anti-S. ictaluri antibody levels. Twenty-one days after the challenge, the HISSI and SSI group antibody levels significantly increased above their corresponding pre-challenge levels. No significant (r(2)=0.0806; P<0.5985) correlation between increased pre-challenge specific serum antibody levels and survival after challenge was demonstrated when analyzing the control and passive immunization groups. The results indicate that both specific anti-S. ictaluri antibodies and non-specific immune responses are important for protection against S. ictaluri.


Audit of the prevalence and investigation of iron deficiency anaemia in patients with heart failure in hospital practice.
Iron deficiency anaemia (IDA) is associated with increased morbidity and mortality in heart failure patients. The aim of our audit was to evaluate the current practice in diagnosis and assessment of IDA in patients admitted with heart failure. We conducted a retrospective audit of patients admitted to our hospital between January 2017 and June 2017 with a diagnosis of heart failure, and obtained data regarding each patient's demographics and anaemic status. We also conducted a qualitative survey to assess healthcare professionals' ability to diagnose IDA, and their knowledge of iron replacement in heart failure patients. Our audit identified 218 heart failure patients, nearly two-thirds (n=138, 63.3%) of which were anaemic. Of the 138 anaemic patients, only 40 had a full haematinic screen compared with 98 who had incomplete investigations (29% vs 71%, p=0.007). Iron studies were the most commonly performed haematinic investigation (n=87, 63%), and over half of these patients were iron deficient (n=49, 56.3%). Only 12 (24.5%) iron deficient patients were prescribed oral iron therapy, while 37 (75.5%) were left without iron replacement (X2=12.8, p=0.0003). Our survey demonstrated a lack of awareness among healthcare professionals with only 19.7% of participants being able to correctly define anaemia and 9.1% being aware of guidelines regarding treatment of IDA. Many patients admitted to hospital with heart failure also have a concomitant diagnosis of anaemia. The aetiology of the underlying anaemia is often poorly investigated, and where IDA is identified it is poorly treated.


Purification and properties of the membrane-bound form of acetylcholinesterase from chicken brain. Evidence for two distinct polypeptide chains.
The major molecular form of acetylcholinesterase (AChE) from chicken brain is a membrane-bound glycoprotein with an apparent sedimentation coefficient of 11.4 S. Analysis of the purified protein by gel filtration, velocity sedimentation, and sodium dodecyl sulfate-gel electrophoresis shows that the solubilized enzyme is a globular tetramer with an apparent Mr = 420,000. This membrane-bound form of AChE is hydrophobic and readily aggregates in the absence of detergent. These aggregates are concentration-dependent, relatively stable in the presence of high salt concentrations, yet readily dissociate upon addition of detergent to the 11.4 S form, indicating that the interactions are hydrophobic. Polyclonal and monoclonal antibodies raised against chicken brain AChE purified by ion exchange chromatography, affinity chromatography, and preparative gel electrophoresis precipitate AChE enzyme activity. However, these antibodies do not cross-react with the enzyme from chicken muscle which preferentially hydrolyses butyrylcholine. Immunoprecipitation of isotopically labeled enzyme molecules from tissue cultured brain cells and analysis by sodium dodecyl sulfate-gel electrophoresis shows that AChE consists of two polypeptide chains with apparent Mr = 105,000 (alpha) and 100,000 (beta) in a 1:1 ratio. Immunoblotting of brain AChE with either the polyclonal or monoclonal antibodies indicates that the alpha and beta chains share antigenic determinants. Furthermore, both polypeptide chains can be labeled with [3H]diisopropyl fluorophosphate, indicating that they each contain a catalytic site. This is the first indication that globular forms of AChE may consist of multiple polypeptide chains.


Binding of 1-nitro[14C]pyrene to DNA and protein in cultured lung macrophages and respiratory tissues.
Binding of 1-nitro[14C]pyrene (1-NP) or its metabolites to cellular DNA and protein in cultures of rabbit alveolar macrophages and lung and tracheal tissues was examined. DNA binding was highest in tracheal tissue (136.9 +/- 18.3 pmol 1-NP/mg DNA). DNA binding in macrophages and lung tissue was one-fifth of the level observed in tracheal tissue. Also, 1-NP was bound to cellular protein in tracheal and lung tissues, and at a lower level in macrophages. Co-cultivation of the macrophages with lung and tracheal tissues decreased the DNA binding in tracheal tissue and increased the protein binding in macrophages. This study shows that lung cells and tissue are capable of binding 1-NP or its metabolites to DNA and protein.


User satisfaction and the readiness-to-use e-health applications in the future in Polish society in the early phase of the COVID-19 pandemic: A cross-sectional study.
The COVID-19 pandemic resulted in the rapid expansion of e-health services in Poland. The main aim of the study was to assess the determinants of user satisfaction and the readiness-to-use e-health applications in Polish society. The paper presents the results of the analysis of the data obtained through a computer-assisted web interviewing survey in a representative sample of 1002 adult Internet users in Poland. The survey was based on a questionnaire consisting of 55 items. The determinants of user satisfaction and the readiness-to-use of e-health solutions were assessed with univariable and hierarchical logistic regression models. E-health services had been used by 60.6% of respondents from the beginning of the epidemic state in Poland to June 2020, when the survey was performed. The hierarchical model showed that user satisfaction with e-health interactions was significantly associated with HL (Health Literacy) and eHL (e-Health Literacy), COVID-19-related conspiracy beliefs score, and using a televisit because of acute symptoms not suggesting COVID-19. Readiness-to-use e-health in the future showed a significant relationship with place of residence, marital status, eHL, the self-assessment of knowledge about preventing COVID-19, the use of televisits for renewing prescriptions, and the level of satisfaction with e-health services. Satisfaction with e-health services depends mainly on the HL, eHL, and conspiracy beliefs of patients. Readiness-to-use e-health in the future is associated with the level of eHL and sociodemographic characteristics, but previous experience with e-health services seems to be the main predictor.


Alkaloids from Alstonia angustifolia.
Six new alkaloids, viz., alstolactone, affinisine oxindole, lagumicine, N(4)-demethylalstonerine, N(4)-demethylalstonerinal, and 10-methoxycathafoline N(4)-oxide, in addition to 36 other known alkaloids, were obtained from the leaf extract of Alstonia angustifolia var. latifolia. The structures of the new alkaloids were determined using NMR and MS analysis.


Resveratrol improves sperm DNA quality and reproductive capacity in type 1 diabetes.
In the coming decades, diabetes mellitus might affect 628 million individuals. Its final impact on male fertility and reproductive outcomes should be considered since the number of adolescents and young adults presenting diabetes is rising. Resveratrol (RES), a polyphenol, is a biological modulator with multitarget and multi-action characteristics. to evaluate if RES is effective against the male reproductive damage caused by type 1 diabetes (DM1), focusing on sperm DNA integrity and reproductive outcome. At 30 dpp (days postpartum), male rats were divided into 7 groups: Sham control (SC); RES vehicle (RV); RES (R); STZ-diabetic (D; induced at 30dpp with 65 mg/kg of streptozotocin); STZ-diabetic + insulin (DI); STZ-diabetic + RES (DR); STZ-diabetic + insulin +RES (DIR). DR, DIR, and R groups received 150mg RES/kg b.w./day by gavage (from 33 to 110dpp). DI and DIR received insulin (from day 5 after DM1 induction until 110dpp). Blood glucose was monitored in different time points. Animals were mated with healthy females. Euthanasia occurred at 110 dpp. DM1 increased lipid peroxidation (testis and epididymis) and sperm DNA fragmentation, alterations of chromatin structure, reduced mitochondrial mass and acrosome integrity, causing a decline in fertility and pregnancy rates. RES improved the parameters. RES, as an adjuvant, activates specific reactions against hyperglycemia, the main trigger of most complications of diabetes, by controlling oxidative stress, probably as a result of SIRT1 activation. We present here more evidences showing its valuable role in diminishing diabetes seriousness to male reproduction, not only to spermatogenesis in the first instance, but also to sperm overall quality and fertility outcomes, regardless of insulin treatment. RES attenuated lipid peroxidation and sperm DNA damage in DM1-induced animals, which positively reflected on male fertility. Our results show RES potential against DM1 complications in male reproduction.


Laparoscopic herniorrhaphy. A preperitoneal tension-free approach.
At the present time laparoscopic herniorrhaphy appears to be successfully performed by utilizing a preperitoneal approach. The major indications are bilaterals hernia and the recurrent hernia. Other routine hernias may be done at the decision of the surgeon and patient depending upon the necessity of rapid return to work and desire to minimize pain. Utilizing this approach, the recurrence rate at the present time is less than 1%, which compares favorably with all other types of repair.


Anisometropia of ocular refractive and biometric measures among 66- to 79-year-old female twins.
To examine the prevalence of anisometropia of spherical refraction (AnisoSR), astigmatism (AnisoAST) and spherical equivalent (AnisoSE) and their associations with spherical refraction (SR), refractive astigmatism (AST), spherical equivalent (SE) and interocular differences of ocular biometric parameters among elderly female twins. Refraction of 117 monozygotic (MZ) and 116 dizygotic (DZ) female twin subjects aged 66-79 years was assessed with an auto-refractor (Topcon AT) and controlled by subjective refraction. Corneal refraction, anterior chamber depth and axial length were measured with a Zeiss IOL Master. Participants with eyes operated for cataract or glaucoma were excluded, but the grade of nuclear opacity was not recorded. The associations between the absolute values of AnisoSR, AnisoAST and AnisoSE with SR, AST, SE, corneal refractive power (CR), corneal astigmatism (CAST), anterior chamber depth (ACD) and axial length (AL) and with their interocular differences were calculated. When calculating the interdependencies of the differences, the real and absolute differences between the right and left eye were used. Means ± standard deviations for AnisoSR, AnisoAST and AnisoSE were 0.67 ± 0.92 D, 0.42 ± 0.41 D and 0.65 ± 0.71 D, respectively. AnisoSR, AnisoAST and AnisoSE >1.0 D were present in 14.7%, 4.2% and 17.7% of cases, respectively. Anisometropia of spherical refraction (AnisoSR), AnisoAST and AnisoSE were higher the more negative the values of SR or SE. Hyperopic ametropia did not increase these anisometropia values. The correlations of AnisoSR and AnisoSE with the absolute values of interocular differences in CR and AL were non-significant. Using the real values of the interocular differences, the respective correlations were significant. The correlation between the real interocular differences in CR and AL was negative (r = -0.258, p < 0.001). Thus, the combined effect of the real interocular differences in CR and AL was a decrease in AnisoSR and AnisoSE (emmetropization). Higher AnisoSR and AnisoSE were associated with more myopic refraction and longer AL. Higher AnisoAST was associated with more negative SR and higher AST and CAST. The negative correlation between real interocular differences in CR and AL indicated their influence of emmetropization in AnisoSR and AnisoSE.


Compression of a polymer chain by a small obstacle: the effect of fluctuations on the escape transition.
We describe the escape transition of an ideal chain compressed between finite-sized obstacles. Three different theoretical methods are used and each provides a similar description of the escape transition, as predicted by earlier and less detailed mean-field theories. The first two methods show that thermal fluctuations near the transition can blur what was previously described as a sharp transition. The last method is an exact calculation of the partition function that shows unambiguously the character of the escape transition. This exact calculation overcomes the inherent uncertainties associated with previous theory and computer simulation.


Differential regulation of glucose transport and transporters by glucose in vascular endothelial and smooth muscle cells.
Hyperglycemia has been implicated in the pathogenesis of both micro- and macrovascular complications in diabetes. Little is known, however, about glucose transporters and their regulation in the vascular system. In this study, the regulation of glucose transporters by glucose was examined in cultured BAECs and BSMCs, and in human arterial smooth muscle cells. Both BAECs and BSMCs transported glucose via the facilitated diffusion transport system. Glucose-transport activity in vascular smooth muscle cells was inversely and reversibly regulated by glucose. Exposure of BSMCs and HSMCs to high glucose decreased Vmax for 2DG and 3-O-MG uptake, whereas Km remained unchanged. The hexose-transport system of BAECs exhibited lower 2DG and 3-O-MG uptake compared with BSMCs and showed little or no adaptation to changes in ambient glucose. Northern blot analysis demonstrated that GLUT1 mRNA levels in BAECs and BSMCs were unaffected by the concentration of glucose in the medium. GLUT2-5 mRNA could not be detected by Northern blot analysis. GLUT1 protein, quantified by Western blot analysis, was more abundant in BSMCs than in BAECs and was decreased by approximately 50% when medium glucose was elevated from 1.2 to 22 mM for 24 h. The alterations in the level of GLUT1 protein correlated with the changes observed in transport activity. These observations suggest differential regulation of glucose transporter in response to glucose between smooth muscle and endothelial cells. The sites of autoregulation may involve translational control and/or the stability of the protein in the smooth muscle cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Main and added effects of heatwaves on hospitalizations for mental and behavioral disorders in a tropical megacity of Vietnam.
Vietnam is highly vulnerable to climate change-related extreme weather events such as heatwaves. This study assesses the association between heatwaves and hospitalizations due to mental and behavioral disorders (MBDs) in Ho Chi Minh City (HCMC). We collected daily MBD hospital admissions data at the HCMC Mental Health Hospital from 2017 to 2019. Heatwaves effects were characterized into the main effect (i.e., the intensity of temperature during heatwaves) and the added effect (i.e., the duration of heatwaves). Time series Poisson regression coupled with a distributed lag linear model (DLM) was used to quantify the 14-day lags effect of heatwaves. Confounders including long-term trend, seasonality, days of the week, holidays, and relative humidity were included in the model. Heatwaves increased all-cause MBD hospitalization by 62% (95%Cl, 36-93%) for the main effect and by 8% (95% Cl, - 3% to 19%) for the added effect. Noticeably, the group aged 18-60 years old was affected by the main effect of the heatwave, while the group aged 61 years and older was affected by the added effect of the heatwave. The effects of heatwaves differed among groups of MBD hospitalizations. The mental and behavioral disorder group due to psychoactive substance use was significantly affected by the main effect of heatwaves (RR:2.21; 95%Cl:1.55-3.15). The group of schizophrenia, schizotypal and delusional disorders were highly vulnerable towards both the main and the added effect of heatwaves with RR = 1.50 (95%CI, 1.20-1.86) and RR = 1.14 (95%CI, 1.01-1.30), respectively.


Use of an impedance threshold device improves short-term outcomes following out-of-hospital cardiac arrest.
An impedance threshold device (ITD) has been developed for the treatment of cardiac arrest to augment circulation to the heart and brain during cardiopulmonary resuscitation (CPR). The ITD has ventilation timing lights that flash at 12 min(-1) to discourage excessive ventilation rates. Implementation of the ITD during conventional manual CPR in a large emergency medical services (EMS) system (Staffordshire, UK) is safe, feasible and will improve short-term survival. ITD use was implemented by the Staffordshire Ambulance Trust, which treats 1600 cardiac arrests per year with 90 advanced life support (ALS) units and an average response time of 6.3 min. During training, rescuers learned to use the ventilation timing lights to discourage hyperventilation. Rescuers applied the device after tracheal intubation. They were trained to allow the chest to recoil fully after each compression. Prospective ITD use in adults receiving conventional manual CPR for non-traumatic cardiac arrest was compared to matched historical controls receiving conventional manual CPR without inspiratory impedance. All received similar ALS care. The primary endpoint was admission to the emergency department (ED) alive following cardiac arrest. Chi-square, Fisher's exact and Kolmogorov-Smirnov tests were used for statistical analyses. Survival (alive upon ED admission) in all patients receiving an ITD (61/181 [34%]) improved by 50% compared to historical controls (180/808 [22%]) (P<0.01). Survival in patients presenting in asystole tripled in the group receiving an ITD (26/76 [34%]) compared with historical controls (39/351 [11%]) (P=0.001). There were no significant adverse events. The ITD was used safely and effectively in a large, diverse EMS system and markedly improved short-term survival for adult patients in non-traumatic cardiac arrest.


The nature of the hepatic receptors involved in vasopressin-induced glycogenolysis.
We have found a close correlation between the known vasopressor potency of arginine vasopressin and fourteen structural analogs, and the ability of these peptides to activate glycogen phosphorylase in isolated rat hepatocytes; there was no relation with the known antidiuretic activity of the analogs. We have also found that the pA2 values characterizing the known antivasopressor capacity of five analogs against vasopressin were close to those obtained for their inhibition of the vasopressin-induced activation of hepatic glycogen phosphorylase. We propose therefore that the hepatic receptors responsible for the glycogenolytic activity of vasopressin share characteristics with and appear therefore related to those responsible for pressor activity in vivo.


Role of transforming growth factor-beta(1) in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosis.
Activation of alveolar macrophages (AM) for tumour necrosis factor production is suppressed initially during the inflammatory response to fibrogenic dusts. We investigated the mechanisms involved in TNF suppression, notably the role of other AM-derived mediators including prostaglandin E(2) (PGE(2)), transforming growth factor-beta(1) (TGF-beta(1)), and interleukin 6 (IL-6). The action of PGE(2) and TGF-beta(1), on AM was different. At physiologically relevant doses (25-300 pg/ml), PGE(2) did not cause significant inhibition of Hpopolysaccharide (Lps)-induced TNF release by AM in vitro but stimulated IL-6 (up to six fold), an inhibitor of AM-derived TNT. In contrast, TGF-beta(1) (0.5-50 ng/ml) inhibited both LPS-induced TNT and IL-6 release by 50% but had no effect on PGE(2) production by AM. To determine the respective contribution of these different inhibitors in TNF suppression, AM from rats exposed to fibrogenic asbestos for weeks were treated with neutralizing antibody against TGF-beta(1) or indomethacin, an inhibitor of PGE(2) synthesis. Treatment of rat AM with anti-TGF-beta(1) but not indomethacin, abrogated the observed TNT suppression. These results suggest that an autocrine, TGF-beta(1)-dependent mechanism is involved in the down-regulation of TNF production by rat AM from animals with lung fibrosis.


A meta-analysis of transcriptomic profiles reveals molecular pathways response to cadmium stress of Gramineae.
As a non-essential heavy metal, cadmium (Cd) is toxic to plants. In the last 15 years, over 70 transcriptome studies have been published to decipher the molecular response mechanism against Cd stress in different plants. To extract generalization results from transcriptomic data across different plants and obtain some hub genes that respond to Cd stress, we carried out a meta-analysis of 32 published datasets. Cluster analysis revealed that plant species played a more decisive role than the media used and exposure time in the transcriptome patterns of plant roots response to Cd. The datasets from a Gramineae-like (GL) group were closer in clustering. 838 DEGs were commonly Cd-regulated in at least nine of 18 GL datasets. Gene ontology and KEGG pathway analyses revealed that oxidative stress-related terms and lignin synthesis-related terms were significantly enriched. Mapman analysis revealed that these common DEGs were mainly involved in regulation, cellular response, secondary metabolism, transport, cell wall and lipid metabolism. In Oryza sativa, 15 DEGs were up-regulated in at least four of five HM (As, Cr, Cd, Hg and Pb) groups, such as Os10g0517500 (methionine gamma-lyase) and Os01g0159800 (bHLH107). Moreover, our datasets can be used to retrieve log2FC value of specific genes across 29 studies (48 datasets), which provides data reference for the subsequent selection of HM-related genes. Our results provide the basis for further understanding of Cd tolerance mechanisms in plants.


Placement of Plantar Plates for Lapidus Arthrodesis: Anatomical Considerations.
The modified Lapidus procedure is an accepted treatment option for patients with moderate to severe hallux valgus. Placing a plate plantar on the tension side of the arthrodesis has been shown to be biomechanically superior and has provided good clinical results. There is some concern about interference of the plantar placed plates on the tendon insertions. The purpose of this study was to determine a "safe zone" for plantar plate placement without irritation of the tendons. Twenty-nine embalmed right feet were used for this study. The anatomy of the insertion of the peroneus longus (PL) tendon and tibialis anterior (TA) tendon on the medial cuneiform and first metatarsal were analyzed. Six different plate designs for plantar plating of the first tarsometatarsal fusion were included. The fit to the bone and contact to tendon insertion were analyzed. The PL showed a main insertion to the first metatarsal and a lesser insertion to the medial cuneiform. The TA inserted onto the medial cuneiform and first metatarsal in all cases in our series. There was a "safe zone" between the TA and PL insertion areas for plate placement. Straight, Y- and U-shaped plates could be placed without compromising the tendon insertion. Depending on the design, even preshaped plates may have to be bent to allow a good fit to the plantar side of the first tarsometatarsal joint. Plantar plating for modified Lapidus arthrodesis can be safely performed, without damaging the plantar tendon insertion area of the PL and TA. The exact knowledge of the anatomy of the plantar region of the tarsometatarsal joint can help to improve plate placement.


Effectiveness of a tailored communication intervention on colonoscopy uptake for firstdegree relatives of colorectal cancer patients: A randomized controlled trial.
To evaluate the effect of a WeChat tailored communication intervention on colonoscopy uptake and health beliefs in Chinese first-degree relatives (FDRs) of colorectal cancer patients. This study employed a single-blinded randomized controlled trial. A total of 188 eligible FDRs were recruited and randomly assigned to the tailored intervention group or control group. Health beliefs were assessed at 1 (T1) and 3 months (T2) postintervention. The colonoscopy uptake was verified by medical records at T2. Data were analyzed using binary logistic regression and generalized estimating equation models. Compared with the participants in the control group, those in the intervention group had a significant improvement in terms of colonoscopy uptake (OR = 2.752, 95% CI: 1.428-5.303, P < 0.01), perceived susceptibility (T1: β = 0.298, 95% CI: 0.052-0.402, P < 0.05; T2: β = 0.251, 95% CI: 0.078-0.424, P < 0.001) and cues to action (T1: β = 0.0.264, 95% CI: 0.138-0.389, P < 0.001; T2: β = 0.327, 95% CI: 0.195-0.459, P < 0.001) and a significant reduction in perceived barriers (T1: β = -0.237, 95% CI: -0.360-0.115, P < 0.01; T2: β = -0.196, 95% CI: -0.331-0.062, P < 0.01). This study broadens the application of tailored communication using novel channels in the context of screening in the at-risk Chinese population. The results provide insights on how to improve the intervention by modifying its components and communication channels.


Analysis and application of RNA binding protein gene pairs to predict the prognosis of gastric cancer.
RNA-binding proteins (RBPs) are closely related to tumors, but little is known about the mechanism of RBPs in tumorigenesis and progression of gastric cancer (GC). As genes do not usually act alone in the pathway deregulation, gene pair combinations are more likely to become stable and accurate biomarkers. The purpose of our research is to establish a novel signature based on RBP gene pairs to predict the prognosis of gastric cancer patients. We downloaded genetic and clinical information from the TCGA and GEO database. TCGA and GSE13911 were used for screening differentially expressed genes (DEGs). The RBP genes were gathered from previous studies and employed to screen out DE-RBP genes after intersecting with DEGs. Samples were classified according to the relative expression of each pair of DE-RBP genes. The univariate Cox regression analysis and random forest were used to identify hub gene pairs to construct signature for predicting the prognosis of gastric cancer. Time-dependent ROC curves and KM survival curves were performed to evaluate the signature. GSEA was performed in TCGA training cohort and GSE62254 testing cohort to analyze enrichment pathways. Finally, the influence of these gene pairs on the prognosis of GC patients was further elucidated respectively through the combination of high and low expression of the two genes in each hub gene pair. We screened out 6 hub RBP gene pairs (COL5A2/FEN1, POP1/GFRA1, EXO1/PLEKHS1, SLC39A10/CHI3L1, MMP7/PPP1R1 B and SLC5A6/BYSL) to predict the prognosis of patients with gastric cancer. Using the optimal cut-off value to divide patients into high-risk and low-risk groups in the training and testing cohort, we found that the overall survival (OS) of the low-risk group was higher than that of the high-risk group (P < 0.05). The area under the ROC curves for 1, 3, and 5 years were (0.659, 0.744, 0.758) and (0.624, 0.650, 0.653) in two cohorts. Univariate and multivariate Cox regression analysis showed that 6 RBP gene pairs signature were independent prognostic factors for gastric cancer (P < 0.05). In addition, the prognostic survival analysis showed that COL5A2-high/FEN1-low, POP1-low/GFRA1-high, EXO1-low/PLEKHS1-low,SLC39A10-high/CHI3L1-low, MMP7-high/PPP1R1 B-low, SLC5A6-low/BYSL-low had worse OS (P < 0.05). And the gene correlation analysis showed that there was no obvious correlation between the genes in each gene pairs except SLC5A6/BYSL and POP1/GFRA1. Finally, GSEA analysis showed that the high-risk group was enriched in tumor migration, invasion and growth-related pathways. Our study identified a novel 6 RBP gene pairs signature to predict the prognosis of gastric cancer patients and provide potential targets for clinical gene therapy.


Eleutherine indica L. accelerates in vivo cutaneous wound healing by stimulating Smad-mediated collagen production.
Eleutherine indica L. has been used for healing of wound, painful and irregular menstruation, dysentery and lesions, and topically used as antiseptic and antimicrobial agent in folk medicine. In the present study, methanolic extracts of Eleutherine indica was subjected to scientific investigation for in-vivo cutaneous wound healing in wistar rat. In-vivo wound healing activity of Eleutherine indica was evaluated by using circular excision experimental models, followed by histopathological and western blot analysis. The healing potential was comparatively assessed with a reference gentamicin sulfate hydrogel (0.01% w/w). Wound contraction measurement, hydroxyproline estimation and western blot for COL3A1, bFGF, Smad-2, -3, -4, and -7 were performed. The methanolic extract of Eleutherine indica showed accelerated wound healing activity as evidenced by fast wound contraction rate and higher hydroxyproline content of granulation tissue. Western blot revealed the Smad-mediated collagen production promoting property of Eleutherine indica methanolic extract. Histopathological examinations also supported the experimental findings. The study revealed that Eleutherine indica promotes wound healing by augmenting Smad-mediated collagen production in wound granulation tissue.


Adrenocortical suppression and other endocrine effects of etomidate.
(+/-) Etomidate is a short-acting general anaesthetic given by the intravenous route. It has strong adrenal suppression capability initially shown in the rat and then observed in man. At present, the drug seems the most effective adrenocortical inhibitor on a molar basis in vitro. 11 beta-hydroxylase is the most sensitive target enzyme; 16 alpha-, 17 alpha-hydroxylase and cholesterol side-chain cleavage are inhibited by higher concentrations. (+) Etomidate was more active than the (+/-) and far more than the (-) stereoisomer. Etomidate blood concentrations greatly exceed those needed to block adrenal steroidogenesis both when used inappropriately by infusion for long-term sedation (such previously unrecognized drug-induced adrenal suppression has often proved fatal in severely-injured patients) and also when given in very low doses as an induction anaesthetic. Reactive ACTH increase is currently observed. Etomidate, in vivo, does not appear to affect testicular steroidogenesis although it shares an imidazole moiety with fungicide phenylimidazoles endowed with such an action. However, testosterone production may be reduced by high concentrations in vitro. Other gonadal hormones seem unchanged. Both basal and stress-induced blood prolactin levels are lowered by etomidate in the rat but probably not in man arguably through interference at brain level where the GABA-benzodiazepine receptor complex could be directly involved. Hence, endocrine and neuroendocrine interferences are unique non-anaesthetic effects of etomidate.


Electrochemical detection of type 2 diabetes mellitus-related SNP via DNA-mediated growth of silver nanoparticles on single walled carbon nanotubes.
Herein, we proposed a new electrochemical sensing strategy for T2DM-related SNP detection via DNA-mediated growth of AgNPs on a SWCNT-modified electrode. Coupled with RNase HII enzyme assisted amplification, this approach could realize T2DM-related SNP assay and be applied in crude extracts of carcinoma pancreatic β-cell lines.


Pyriform Aperture Augmentation as An Adjunct to Rhinoplasty.
Skeletal deficiency in the central midface impacts nasal aesthetics. This lack of lower face projection can be corrected by alloplastic augmentation of the pyriform aperture. Creating convexity in the deficient midface will make the nose seem less prominent. Augmentation of the pyriform aperture is, therefore, often a useful adjunct during the rhinoplasty procedure. Augmenting the skeleton in this area can alter the projection of the nasal base, the nasolabial angle, and the vertical plane of the lip. The implant design and surgical techniques described here are extensions of others' previous efforts to improve paranasal aesthetics.


Identification of softness syndrome-associated candidate genes and DNA sequence variation in the sea squirt, Halocynthia roretzi.
The mortality of sea squirts, Halocynthia roretzi, with softness syndrome threatens the sea squirt aquaculture industry in Asian countries. The molecular approach to understanding the pathogenesis of softness syndrome began with differential gene expression analysis of tissues from normal and dying organisms. In the present study, we show that the expression of Halocynthia roretzi metalloproteinase (HrMMP) was significantly upregulated in the tissues of dying organisms through screening of differentially expressed genes, reverse transcription-polymerase chain reaction (RT-PCR), and real-time PCR. HrMMP is composed of 482 amino acids, contains a conserved domain found in the astacin family, and has typical metalloproteinase activity. To discriminate between the differential expression of the HrMMP gene in normal and dying organisms, we cloned the HrMMP gene promoter and identified a polymorphism in the HrMMP promoter region that resulted in distinct polymorphisms (G/T) at position - 308 bp. These results suggest that organisms with the GT genotype may have more resistance to softness syndrome than those with the TT genotype. These findings suggest that the HrMMP promoter polymorphism may be associated with an increased risk of softness syndrome in cultivated sea squirts and should be evaluated as a candidate molecular marker for the selective breeding of softness syndrome-resistant sea squirts.


Pharmacokinetics of recombinant human lipocalin-type prostaglandin D synthase/beta-trace in canine.
Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is identical to beta-trace, a major protein in human cerebrospinal fluid (CSF), and acts as both a PGD(2)-producing enzyme and as an extracellular transporter for lipophilic ligands. In this study, we investigated the pharmacokinetics of recombinant human L-PGDS (rh-L-PGDS) in canines. After an intravenous bolus injection of rh-L-PGDS, the serum concentration decreased bi-exponentially with a half-life of the terminal line phase of 0.77h, which was markedly shorter than that of other proteins with the same molecular weight as that of rh-L-PGDS. The distribution volume was 55.4ml/kg, which was close to the volume of canine circulation plasma, indicating that the administrated rh-L-PGDS was distributed mainly in the blood. Only 10.3% of the administered rh-L-PGDS was excreted to the urine, suggesting that rh-L-PGDS was actively degraded within the body. After an intrathecal injection, the peak serum concentration of rh-L-PGDS was observed at 4-5h. The area under the plasma concentration-time curve obtained for 12h after the intrathecal injection was one third of the value for 3h after the intravenous injection, suggesting that at least one third of the intrathecally injected rh-L-PGDS shifted to the blood.


Genetic analysis of the murine mu opioid receptor: increased complexity of Oprm gene splicing.
Evidence exists that mu analgesics such as morphine, methadone and fentanyl may act through distinct mu opioid receptor mechanisms. It has been proposed that the functional diversity of mu opioid receptors may be related to alternative splicing of the Oprm gene. Although a number of mu opioid receptor mRNA splice variants have been reported, their biological relevance has been controversial, due in part to their very low abundance and a general lack of validation from independent laboratories. We have identified 11 of 17 proposed exons as well as the majority of exon combinations used to make 21 differentially spliced Oprm mRNAs from mouse whole brain cDNA, using polymerase chain reaction (PCR) conditions different from those used by the single other group that has reported multiple splice forms. Alternative splicing was shown to occur at both the 5' and 3' termini. Moreover, verification of a short variant, containing exons 1 and 4 only, suggests that splicing also occurs directly between 5' and 3' exons. Notably, a novel splice variant, MOR-1T, demonstrates for the first time that exon 4 can be used in combination with further downstream exons to make the 3'-end of MOR-1 splice variants. The putative protein encoded by MOR-1T is predicted to be identical to that of MOR-1, implying that the MOR-1 protein can be generated from at least five differentially spliced mRNAs. Our results support the view that the Oprm gene undergoes extensive alternative splicing, as a likely major contributor to the diversity of mu opioid receptors.


Nonbacterial thrombotic endocarditis demonstrated by repeat echocardiography.
We report a case of nonbacterial thrombotic endocarditis (NBTE) in a patient with bladder cancer presenting with multiple cerebral infarctions. Initial transthoracic and transesophageal echocardiography did not show any abnormalities. However, repeat transthoracic and transesophageal echocardiography demonstrated a vegetation on the anterior leaflet of the mitral valve with mild mitral regurgitation and no evidence of leaflet destruction. Persistent high-grade fevers and leukocytosis were observed. The patient was suspected to have infective endocarditis. However, abdominal ultrasound and computed tomography scan revealed multiple metastatic masses, and serial blood cultures were negative. The patient was ultimately diagnosed with NBTE associated with multiple metastases of bladder cancer. This case suggests that even if echocardiography does not initially demonstrate any abnormalities in patients with embolism, it must be repeated at the recurrence of embolism, and that even if clinical signs of infection are documented, NBTE should be suspected in any cancer patient with thromboembolic events.


Thirteen treated of acute renal failure secondary to multiple myeloma with high cut off filters.
Multiple myeloma (MM) is a haematological tumour that is characterised by uncontrolled proliferation of plasma cells and a significant volume of serum free light chains (sFLCs), which can cause acute renal failure due to intratubular precipitation, resulting in cast nephropathy. Acute renal failure is a complication that can arise in more than 20% of patients with multiple myeloma, half of which will require dialysis. We report our experience with 13 patients who were treated with dialysis using high cut off filters (HCO) between July 2011 and February 2015. A total of 6 consecutive 6-hour sessions were performed using a 2.1 m(2) HCO filter (Theralite® by Gambro®). Afterwards, further 6-hour sessions were continued on alternate days. A total of 151 sessions were conducted, with an average of 11.6 sessions per patient (range 6-27). The treatment proved to be effective in removing both kappa and lambda sFLCs, resulting in a 93.7% fall in sFLCs by the end of treatment. The average reduction was 57.7% per dialysis session. 10 out of the 13 cases recovered sufficient renal function to become independent of dialysis. There were no major changes in albumin levels using an infusion protocol of 2 50-mL vials of 20% albumin at the end of the dialysis session. Combination treatment with chemotherapy and long dialysis with HCO filters was effective in reducing the sFLC levels and recovering sufficient renal function in 77% of cases. With HCO filters, significant cost savings are achieved, contrary to what was previously believed.


Within- and between-therapist agreement on personalized parameters for robot-assisted gait therapy: the challenge of adjusting robotic assistance.
Stationary robotic gait trainers usually allow for adjustment of training parameters, including gait speed, body weight support and robotic assistance, to personalize therapy. Consequently, therapists personalize parameter settings to pursue a relevant therapy goal for each patient. Previous work has shown that the choice of parameters influences the behavior of patients. At the same time, randomized clinical trials usually do not report the applied settings and do not consider them in the interpretation of their results. The choice of adequate parameter settings therefore remains one of the major challenges that therapists face in everyday clinical practice. For therapy to be most effective, personalization should ideally result in repeatable parameter settings for repeatable therapy situations, irrespective of the therapist who adjusts the parameters. This has not yet been investigated. Therefore, the aim of the present study was to investigate the agreement of parameter settings from session to session within a therapist and between two different therapists in children and adolescents undergoing robot-assisted gait training. Fourteen patients walked in the robotic gait trainer Lokomat on 2 days. Two therapists from a pool of 5 therapists independently personalized gait speed, bodyweight support and robotic assistance for a moderately and a vigorously intensive therapy task. There was a very high agreement within and between therapists for the parameters gait speed and bodyweight support, but a substantially lower agreement for robotic assistance. These findings imply that therapists perform consistently at setting parameters that have a very clear and visible clinical effect (e.g. walking speed and bodyweight support). However, they have more difficulties with robotic assistance, which has a more ambiguous effect because patients may respond differently to changes. Future work should therefore focus on better understanding patient reactions to changes in robotic assistance and especially on how instructions can be employed to steer these reactions. To improve the agreement, we propose that therapists link their choice of robotic assistance to the individual therapy goals of the patients and closely guide the patients during walking with instructions.


Transcriptional control of transglutaminase 2 expression in mouse apoptotic thymocytes.
Transglutaminase 2 (TGM2) is a ubiquitously expressed multifunctional protein, which participates in various biological processes including thymocyte apoptosis. As a result, the transcriptional regulation of the gene is complex and must depend on the cell type. Previous studies from our laboratory have shown that in dying thymocytes the expression of Tgm2 is induced by external signals derived from engulfing macrophages, such as retinoids, transforming growth factor (TGF)-β and adenosine, the latter triggering the adenylate cyclase signaling pathway. The existence of TGF-β and retinoid responsive elements in the promoter region of Tgm2 has already been reported, but the intergenic regulatory elements participating in the regulation of Tgm2 have not yet been identified. Here we used publicly available results from DNase I hypersensitivity analysis followed by deep sequencing and chromatin immunoprecipitation followed by deep sequencing against CCCTC-binding factor (CTCF), H3K4me3, H3K4me1 and H3K27ac to map a putative regulatory element set for Tgm2 in thymocytes. By measuring eRNA expressions of these putative enhancers in retinoid, rTGF-β or dibutiryl cAMP-exposed thymocytes we determined which of them are functional. By applying ChIP-qPCR against SMAD4, retinoic acid receptor, retinoid X receptor, cAMP response element binding protein, P300 and H3K27ac under the same conditions, we identified two enhancers of Tgm2, which seem to act as integrators of the TGF-β, retinoid and adenylate cyclase signaling pathways in dying thymocytes. Our study describes a novel strategy to identify and characterize the signal-specific functional enhancer set of a gene by integrating genome-wide datasets and measuring the production of enhancer specific RNA molecules.


Ratiometric electrochemical immunoassay based on internal reference value for reproducible and sensitive detection of tumor marker.
A ratiometric assay in an electrochemical immunosensor for tumor marker, herein carcinoembryonic antigen (CEA) was chosen as a model analyte, was developed to improve simplicity and accuracy. The immunosensor was fabricated via the simple expedient way of using Polythionine-gold (PTh-Au) as electrode modified material to be an internal reference signal and K3[Fe(CN)6] in electrolyte as an indicator signal. When the CEA was fixed on the modified electrode via immunoreaction, only the indicator signal sensitively altered; by contrast, the internal reference signal of PTh-Au remained constant at a suitable pH of the electrolyte. The ratio between the alterations of the indicator signal of K3[Fe(CN)6] and the constant internal reference signal can be used to monitor the concentration of CEA reliably, reproducibly, and sensitively. The prepared ratiometric electrochemical immunosensor could detect CEA with good specificity within a wide linear range from 0.005ng/ml to 40ng/ml with a detection limit of 2.2pg/ml. Additionally, experimental results confirm that our proposed method is practical. Thus, this method can expand to recognize and test other protein markers.


CYFRA 21-1 as a tool for distant metastasis detection in lung cancer.
A study to analyse tumor markers (CEA, CA125, CA15.3, CA19.9, CYFRA 21-1, and NSE) for metastasis detection in lung cancer patients. Serum tumor markers from 73 lung cancer patients were measured before they were diagnosed. After lung cancer diagnosis, tumor markers were analyzed for the detection of distant metastases. In NSCLC patients CYFRA 21-1 and NSE showed differences between stage IV and any of the other stages, p < 0.05. The accuracy for metastasis detection was AUC = 81.5 % for CYFRA 21-1 and AUC = 78.6 % for < 0.05) were independent predictors for metastasis presence. No tumor marker showed significant differences according to stages in SCLC patients. CYFRA 21-1 could be used as a screening tool for metastasis detection in lung cancer patients without symptoms of metastasis as well as CYFRA 21-1 and NSE in NSCLC patients.


Maple sap predominant microbial contaminants are correlated with the physicochemical and sensorial properties of maple syrup.
Maple sap processing and microbial contamination are significant aspects that affect maple syrup quality. In this study, two sample sets from 2005 and 2008 were used to assess the maple syrup quality variation and its relationship to microbial populations, with respect to processing, production site and harvesting period. The abundance of maple sap predominant bacteria (Pseudomonas fluorescens group and two subgroups, Rahnella spp., Janthinobacterium spp., Leuconostoc mesenteroides) and yeast (Mrakia spp., Mrakiella spp.,Guehomyces pullulans) was assessed by quantitative PCR. Maple syrup properties were analyzed by physicochemical and sensorial methods. Results indicate that P. fluorescens, Mrakia spp., Mrakiella spp. G. pullulans and Rahnella spp. are stable contaminants of maple sap, as they were found for every production site throughout the flow period. Multiple factor analysis reports a link between the relative abundance of P. fluorescens group and Mrakia spp. in maple sap with maple and vanilla odor as well as flavor of maple syrup. This evidence supports the contribution of these microorganisms or a consortium of predominant microbial contaminants to the characteristic properties of maple syrup.


Personal growth and psychological distress in advanced breast cancer.
The experience of posttraumatic growth following breast cancer, its association with psychological distress and the predictive value of psychological distress, sociodemographic and clinical characteristics of cancer patients in their personal growth. The Posttraumatic Growth Inventory and the Greek version of the Hospital Depression and Anxiety Scale (G-HADS) were administered to 100 breast cancer patients. Sociodemographic and clinical characteristics were recorded. The analysis showed that significant associations were found between PTGI-Total patients' age (p=0.001), and being married (p=0.007). Moreover, significant negative association was observed between PTGI-II ("New Possibilities") and HADS-Depression (r=-0.314, p<0.05). Multiple regression analyses showed that age is a significant predictor of PTGI-II ("New Possibilities") (p=0.005), PTGI-V ("Appreciation of Life") (p=0.0005) and PTGI-Total (p=0.037), while marital status is a significant predictor of PTGI-Total (p=0.009). Specific patients' characteristics, such as young age and being with a partner, influence the experience of posttraumatic growth in breast cancer patients.


Identifying neonatal adverse events in preterm and term infants using a paediatric trigger tool.
To explore the incidence and characteristics of inpatient neonatal adverse events in a Swedish setting. A retrospective record review, using a trigger tool, performed by registered nurses and a neonatologist, at a University Hospital. The identified adverse events were categorised by, for example, preventability, severity and time of occurrence. A random selection of 150 admissions representing 3531 patient days were reviewed (mean [SD] birthweight 2620 [1120]g). Three hundred and sixty adverse events were identified in 78 (52.0%) infants, and 305 (84.7%) of these were assessed as being preventable. The overall adverse event rate was 240 per 100 admissions and 102.0 per 1000 patient days. Preterm infants had a higher rate than term infants (353 versus 79 per 100 admissions, p = 0.001); however, with regard to the length of stay, the rates were similar. Most adverse events were temporary and less severe (n = 338/360, 93.9%) and the most common type involved harm to skin, tissue or blood vessels (n = 163/360, 45.3%). Forty percent (n = 145) of adverse events occurred within the first week of admission. Adverse events were common in neonatal care, and many occurred during the first days of treatment. Characterisation of adverse events may provide focus areas for improvements in patient safety.


Veno-occlusive disease of the liver in right-sided Wilms' tumours.
Veno-occlusive disease of the liver (VOD) is an important complication in children with Wilms' tumour. Although in most patients this complication resolves uneventfully, fatal cases have been reported. Several observations strongly suggest that actinomycin-D is the likeliest cause of VOD in Wilms' tumour, but VOD seems to be rather uncommon in other malignancies treated with chemotherapy including actinomycin-D. The present case of VOD and the review of the literature stress the pathogenetic and clinical implications of VOD in the presence of a Wilms' tumour treated with actinomycin-D, originating in the right kidney. Greater awareness of this 'predisposing factor' may alert paediatricians to the presence of minimal signs of the syndrome.


Endoscopic balloon dilation of colorectal strictures complicating Crohn's disease: a multicenter study.
While endoscopic balloon dilation (EBD) is widely used to manage ileal strictures, EBD of colorectal strictures remains poorly investigated in Crohn's disease (CD). We performed a retrospective study that included all consecutive CD patients who underwent EBD for native or anastomotic colorectal strictures in 9 tertiary centers between 1999 and 2018. Factors associated with EBD failure were also investigated by logistic regression. Fifty-seven patients (25 women, median age: 36 years (InterQuartile Range, 31-48) were included. Among the 60 strictures, 52 (87%) were native, 39 (65%) measured < 5 cm and the most frequent location was the left colon (27%). Fifty-seven (95%) were non-passable by the scope and 35 (58%) were ulcerated. Among the 161 EBDs performed (median number of dilations per stricture: 2, IQR 1-3), technical and clinical success were achieved for 79% (n = 116/147) and 77% (n = 88/115), respectively. One perforation occurred (0.6% per EDB and 2% per patient). After a median follow-up of 4.3 years (IQR 2.0-8.4), 24 patients (42%) underwent colonic resection and 24 (42%) were asymptomatic without surgery. One colon lymphoma and one colorectal cancer were diagnosed (3.5% of patients) from endoscopic biopsies and at the time of surgery, respectively. No factor was associated with technical or clinical success. EDB of CD-associated colorectal strictures is feasible, efficient and safe, with more than 40% becoming asymptomatic without surgery.


Abdominal aortic coarctation, renovascular, hypertension, and neurofibromatosis.
Abdominal aortic coarctation and renal artery stenosis associated with neurofibromatosis is an unusual cause of renovascular hypertension in children and young adults. Sustained hypertension despite pharmacological treatment carries significant end-organ deterioration, failure to thrive, and potentially lethal complications. Timely arterial reconstruction can render these children normotensive, allowing normal development and reducing long-term morbidity. Progression of the arterial occlusive process, however, may occur after surgery. Therefore, careful follow-up is mandatory following aortorenal reconstruction in children with neurofibromatosis.


Lipid peroxidation and human cataractogenesis in diabetes and severe myopia.
To investigate the role of lipid peroxidation in human cataract, malondialdehyde, a breakdown product of lipid peroxidation, was measured in clear and cataractous lenses from normal subjects, and in cataractous lenses from diabetics and from subjects with severe myopia. The cataractous lenses contained more malondialdehyde than did clear lenses and the level was higher in diabetes and severe myopia than in the idiopathic forms. This indicates that lipid peroxidation may be involved in the development of senile cataract and, as a direct consequence of retinal damage, also in the pathogenesis of cataract in diabetes and in severe myopia.


Demography and life-history parameters of mantled howler monkeys at La Flor de Catemaco: 20 years post-translocation.
Translocations usually aim at maintaining and enhancing wild populations. Thus, the long-term monitoring of translocated individuals is critical for assessing translocation success. In this study, we report the demographic and life-history parameters of mantled howler monkeys that were translocated to La Flor de Catemaco (Los Tuxtlas, Mexico) to determine the success of the translocation process. Nine individuals belonging to two social groups living in areas that were going to be destroyed were released into La Flor de Catemaco between 2002 and 2004. Before 2022 there were no resident monkeys at the site. From January 2012 to December 2021, we recorded births, deaths, migrations, and group formation (1535 sampling days). The population grew until reaching 35 mantled howler monkeys. Two new groups including both individuals born at the site and migrants were founded. Mean ± SD group size was 8.1 ± 1.1 individuals. We recorded 42 births and 14 deaths, mostly of young infants (< 6 months of age). We recorded emigrations and immigrations of adult and immature individuals as well as several instances of individuals that remained and reproduced in their natal groups. Mean female age at first birth was 57.8 ± 18.5 months, interbirth intervals were 23.3 ± 11.3 months, and birth rates were 0.5 ± 0.2 births per female per year. The growth and persistence of the groups at the site, as well as similarity in demographic and life-history parameters between this and unmanaged populations, suggest that mantled howler monkeys living at La Flor de Catemaco represent a stable population and thus that this was a successful translocation.


Liver Receptor homolog-1 Regulates Apoptosis of Bovine Ovarian Granulosa Cells by Progestogen Receptor Signaling Pathway.
The purpose of the present investigation was to assess the function of LRH-1 on GCs and the mechanisms involved. Here, LRH- was highly expressed in the bovine GCs of atretic follicles. Treatment with 50 μM of LRH-1 agonist (DLPC) significantly induced the expression of LRH-1 (p < 0.05). In particular, LRH-1 activation blocked the progestogen receptor signaling pathway via downregulating progesterone production and progestogen receptor levels (p < 0.05), but had no effect on 17 beta-estradiol synthesis. Meanwhile, LRH-1 activation promoted the apoptosis of GCs and increased the activity of caspase 3 (p < 0.05). Importantly, upregulating the progestogen receptor signaling pathway with progestogen could attenuate the LRH-1-induced proapoptotic effect. Moreover, treatment with progestogen decreased the activity of the proapoptotic gene caspase 3 and increased the expression of antiapoptotic gene Bcl2 in LRH-1 activated GCs (p < 0.05). Taken together, these results demonstrate that LRH-1 might be dependent on the progestogen receptor signaling pathway to modulate bovine follicular atresia.


Ischemic and excitotoxic brain injury is enhanced in mice lacking the p55 tumor necrosis factor receptor.
Ischemic and excitotoxic insults to the brain induce rapid production of tumor necrosis factor-alpha (TNF), but the role of TNF in neuronal responses to brain injury are unclear. Two different TNF receptors (p55 and p75) are expressed in neurons and glia. To understand the role of TNF in brain injury, we generated mice that lack p55, p75, or both receptors. We report that neuronal damage after focal cerebral ischemia-reperfusion is significantly increased in mice lacking p55 receptors (85+/-7 mm3 infarct volume; mean +/- SD) compared with wild-type mice (70+/-8 mm3) and mice lacking p75 receptors (72+/-6 mm3). Moreover, mice lacking p55 receptors exhibited increased degeneration of CA3 hippocampal neurons after administration of the excitotoxin kainic acid compared with wild-type mice and mice lacking p75 receptors. When taken together with recent data showing that TNF can prevent apoptosis of cultured neurons exposed to oxidative and metabolic insults, our findings suggest that TNF plays a neuroprotective role after acute brain insults.


Emission of volatile organic compounds from landfill working surfaces: Formation potential of ozone and secondary organic aerosols.
The working surface of landfills is an important source of volatile organic compounds (VOCs), which have received increasing attention because of their role in potentially forming ozone and secondary organic aerosols (SOAs). In this study, 99 monitoring datasets on VOC emissions from a landfill working surface were obtained in 9 months and used to evaluate their ozone formation potential (OFP) and SOA formation potential (SOAFP) from a statistical perspective and compared using various methods. December was found to have the highest total OFP and SOAFP caused by VOC emissions from the landfill working surface. Both the propylene equivalent concentration (PEC) and maximum incremental reactivity (MIR) methods indicated that oxygenated compounds, especially ethanol, contributed the most to the OFP, accounting for 16.1 %-95.4 % and 44.9 %-98.6 % of the total OFP during the entire observation period, respectively. The fraction aerosol coefficient (FAC) method highlighted the effect of aromatic hydrocarbons which contributed to over 97 % of the total SOAFP. In contrast, the SOA potential (SOAP) method indicated that both aromatic hydrocarbons and oxygenated compounds play important roles, contributing 26.6 %-93.9 % and 21.6 %-73.4 % of the total SOAFP, respectively. Based on their mechanisms and comprehensiveness, PEC and SOAP methods are considered more appropriate for evaluating the OFP and SOAFP of VOCs released from landfill working surfaces. The annual total OFP and SOAFP of VOCs from landfill working surfaces of China in 2020 were thus estimated as 1.5 × 104 t and 135 t, respectively, with high variations among different regions along with the population, waste management system, and the amount of landfilled waste. This study provides a comprehensive understanding of the potential impacts and evaluation methods of local waste landfills in the atmospheric environment from a statistical perspective.


A glucose bio-battery prototype based on a GDH/poly(methylene blue) bioanode and a graphite cathode with an iodide/tri-iodide redox couple.
A glucose bio-battery prototype independent of oxygen is proposed based on a glucose dehydrogenase (GDH) bioanode and a graphite cathode with an iodide/tri-iodide redox couple. At the bioanode, a NADH electrocatalyst, poly(methylene blue) (PMB), which can be easily grown on the electrode (screen-printed carbon paste electrode, SPCE) by electrodeposition, is harnessed and engineered. We find that carboxylated multi-walled carbon nanotubes (MWCNTs) are capable of significantly increasing the deposition amount of PMB and thus enhancing the PMB's electrocatalysis of NADH oxidation and the glucose bio-battery's performance. The choice of the iodide/tri-iodide redox couple eliminates the dependence of oxygen for this bio-battery, thus enabling the bio-battery with a constant current-output feature similar to that of the solar cells. The present glucose bio-battery prototype can attain a maximum power density of 2.4 μW/cm(2) at 25 °C.


Muscimol microinjected in the arcuate nucleus affects metabolism, body temperature & ventilation.
Effects of microinjection of 2 doses of γ-aminobutyric acid (GABA)A receptor agonist, muscimol (M), into the hypothalamic arcuate nucleus on oxygen consumption and control of ventilation over time and body temperature (BT) at the end of the experiment were compared in adult male and female rats. Relative to cerebrospinal fluid (CSF, 0 nmol), BT was decreased only in male rats with both doses of M, while in female rats, the 5 nmol dose depressed oxygen consumption. Ventilation was depressed by 5 nmol M in male and 10 nmol M in female rats by decreasing tidal volume. M did not affect the ventilatory response of male or female rats to hypoxia, whereas in females 5 and 10 nmol M and in males 10 nmol M depressed the ventilatory response to hypercapnia. Thus, in rats GABAA receptors in the arcuate nucleus modulate BT, oxygen consumption, and ventilation in air and in response to hypercapnia in a sexually dimorphic manner.


Cloning and molecular characterization of three genes, including two genes encoding serine hydroxymethyltransferases, whose inactivation is required to render yeast auxotrophic for glycine.
The genes encoding both the cytosolic and mitochondrial serine hydroxymethyltransferases (SHM2 and SHM1, respectively) and a third unidentified gene of the yeast Saccharomyces cerevisiae have been isolated and their nucleotide sequences determined. Analysis of the predicted amino acid sequence of the amino-terminal regions, sequence comparison with other genes encoding SHMT enzymes, and subcellular fractionation studies all suggested that the SHM1 gene encodes the mitochondrial SHMT, while the SHM2 gene encodes the cytosolic enzyme. The SHM2 gene but not the SHM1 gene has putative GCN4 sites upstream of the putative TATA box, suggesting regulation of its transcription by the general amino acid control system. Yeast mutants with disruptions at each SHM gene and in both genes were constructed and all mutants had the same growth requirements as the parental strains. Mutagenesis of the double-disrupted, shm1 shm2 yeast yielded strains of a single complementation group that are auxotrophic for glycine. Complementation of the glycine auxotrophy using a yeast genomic library retrieved the SHM1 and SHM2 genes and a third gene designated GLY1. Gene disruption studies demonstrated that inactivation of SHM1, SHM2, and GLY1 is required to yield yeast that are completely auxotrophic for glycine.