Pervasive within-species spatial repulsion among adult tropical trees.
For species to coexist, performance must decline as the density of conspecific individuals increases. Although evidence for such conspecific negative density dependence (CNDD) exists in forests, the within-species spatial repulsion it should produce has rarely been demonstrated in adults. In this study, we show that in comparison to a null model of stochastic birth, death, and limited dispersal, the adults of dozens of tropical forest tree species show strong spatial repulsion, some to surprising distances of approximately 100 meters. We used simulations to show that such strong repulsion can only occur if CNDD considerably exceeds heterospecific negative density dependence-an even stronger condition required for coexistence-and that large-scale repulsion can indeed result from small-scale CNDD. These results demonstrate substantial niche differences between species that may stabilize species diversity.


Cytofluorometric study of nuclear DNA in the epidermis of keratotic dermatoses.
The cell cycle duration of basal cells in the epidermis of keratotic dermatoses was investigated with cytofluorometric method. In normal epidermis, the relative time spent in each phase was 85.1% (G1), 13.1% (S) and 1.8% (G2 + M). The relative time in ichthyosis vulgaris epidermis was similar to that in normal epidermis. In the case of psoriasis and non-bullous congenital ichthyosiform erythroderma, the relative number of S phase cells was more than that in normal epidermis. In psoriatic epidermis, nuclear protein value was highest not only in G1 fraction of basal cells but in differentiating cells.


Prediction of survival of preoperative colorectal patients: A new tool to assess the interaction of nutritional status and inflammation.
Colorectal cancer (CRC) is responsible for the second leading cause of cancer death worldwide. Thus, the aim of this study was to investigate the application of a new nutritional status and inflammatory tool to predict overall survival (OS) in patients with CRC in the preoperative period. Retrospective cohort study with CRC patients of both sexes treated at a hospital unit, aged ≥20 years. Data were extracted between 2007 and 2015. Multivariate Cox's models were employed to predict OS utilizing a new grade classification system (body mass index vs. percentage weight loss - BMI/%WL), inflammatory markers and clinical data. We evaluated 361 patients. BMI/%WL grade 3-4 (HR: 2.01; p = 0.001; 95% CI: 1.34-3.02) were independent predictors of poor OS. Moreover, BMI/%WL grade 3-4 + neutrophil-to-lymphocyte ratio (NLR) ≥2.4 (HR: 2.79; p = 0.001; 95% CI: 1.54-5.03) increased the death risk in 5-years. However, low NLR (<2.4) altered the OS prognostic ability of the BMI/%WL (HR: 1.72; p = 0.099; 95% CI: 0.90-3.28). BMI/%WL was independent predictors of poor OS and the interaction with NLR produced an adjustment effect. These associated tools may be useful in the clinical management of preoperative patients with CRC.


Stromal androgen signaling acts as tumor niches to drive prostatic basal epithelial progenitor-initiated oncogenesis.
The androgen receptor (AR)-signaling pathways are essential for prostate tumorigenesis. Although significant effort has been devoted to directly targeting AR-expressing tumor cells, these therapies failed in most prostate cancer patients. Here, we demonstrate that loss of AR in stromal sonic-hedgehog Gli1-lineage cells diminishes prostate epithelial oncogenesis and tumor development using in vivo assays and mouse models. Single-cell RNA sequencing and other analyses identified a robust increase of insulin-like growth factor (IGF) binding protein 3 expression in AR-deficient stroma through attenuation of AR suppression on Sp1-regulated transcription, which further inhibits IGF1-induced Wnt/β-catenin activation in adjacent basal epithelial cells and represses their oncogenic growth and tumor development. Epithelial organoids from stromal AR-deficient mice can regain IGF1-induced oncogenic growth. Loss of human prostate tumor basal cell signatures reveals in basal cells of stromal AR-deficient mice. These data demonstrate a distinct mechanism for prostate tumorigenesis and implicate co-targeting stromal and epithelial AR-signaling for prostate cancer.


Virtual screening for potential discoidin domain receptor 1 (DDR1) inhibitors based on structural assessment.
Discoidin domain receptor 1 (DDR1) (EC Number 184.108.40.206) has recently been considered as a promising therapeutic target for idiopathic pulmonary fibrosis (IPF). However, none of the currently discovered DDR1 inhibitors have been included in clinical studies due to low target specificity or druggability limitations, necessitating various approaches to develop novel DDR1 inhibitors. In this study, to assure target specificity, a docking assessment of the DDR1 crystal structures was undertaken to find the well-differentiated crystal structure, and 4CKR was identified among many crystal structures. Then, using the best pharmacophore model and molecular docking, virtual screening of the ChEMBL database was done, and five potential molecules were identified as promising inhibitors of DDR1. Subsequently, all hit compound complex systems were validated using molecular dynamics simulations and MM/PBSA methods to assess the stability of the system after ligand binding to DDR1. Based on molecular dynamics simulations and hydrogen-bonding occupancy analysis, the DDR1-Cpd2, DDR1-Cpd17, and DDR1-Cpd18 complex systems exhibited superior stability compared to the DDR1-Cpd1 and DDR-Cpd33 complex systems. Meanwhile, when targeting DDR1, the descending order of the five hit molecules' binding free energies was Cpd17 (- 145.820 kJ/mol) > Cpd2 (- 131.818 kJ/mol) > Cpd18 (- 130.692 kJ/mol) > Cpd33 (- 129.175 kJ/mol) > Cpd1 (- 126.103 kJ/mol). Among them, Cpd2, Cpd17, and Cpd18 showed improved binding characteristics, indicating that they may be potential DDR1 inhibitors. In this research, we developed a high-hit rate, effective screening method that serves as a theoretical guide for finding DDR1 inhibitors for the development of IPF therapeutics.


Association of the serum metabolomic profile by nuclear magnetic resonance spectroscopy with sperm parameters: a cross-sectional study of 325 men.
To determine whether 155 circulating metabolic measures relevant to lifestyle and metabolic health are associated with sperm parameters, as measured by concentration, motility, and total motile sperm count (TMSC). Cross sectional. University hospital. Three hundred twenty-five men prospectively recruited between April 1, 2017 and March 31, 2019. Detailed demographic, lifestyle, fertility, medical history, and semen analysis with quantification of nonfasting serum lipids, lipoprotein subclasses, and low-molecular weight metabolites (including amino acids, glycolysis, and inflammatory markers) by nuclear magnetic resonance (NMR) spectroscopy. Association of serum metabolic profiles with sperm parameters. The age of the participants was mean 37.2 years, with a median sperm concentration of 35 million/mL and median motility of 53%. Of these men, 76% had a TMSC >15 million, 10% had 5-15 million, and 14% had <5 million. In both univariate and confounder adjusted analyses, an extensive range of lipids and lipoproteins, glycolysis-related metabolites, amino acids, ketone bodies, creatinine, or albumin showed no strong statistically significant association with sperm concentration, motility, or the odds of having a reduced or low TMSC. Higher levels of glycolysis metabolites and ketone bodies were associated with an increased odds of TMSC <15 million compared with ≥15 million (odds ratios of ∼1.2-1.3), and several lipids/lipoprotein concentrations appeared to protect against very low TMSC (<5 million compared with ≥5 million) with odds ratios of ∼0.8 or greater. Several metabolites exhibited potentially clinically relevant strength of association with the odds of a low TMSC and warrant replication.


Correlates of excessive Pokemon Go playing among medical students.
A new virus "Pokémon GO" is infecting Homo sapiens at an exponential rate. The symptoms include swaying your cell phone in air and focusing in blankness, straying into the unknown in search "Pikachu". In the "Pokedemiological" triad, the host is a medical student, agent is Pokémon GO, and the environment is a chaos of childhood fantasies and peer pressure turning into a vicious cycle of addiction, stress, anxiety, and depression. The aim was to study the correlates of excessive playing of Pokemon Go in medical students. By purposive sampling, fifty MBBS students who were regularly playing Pokémon GO for more than 2 weeks and equal number of age-and sex-matched students who were not playing any computer games were included in this study with their consent. They were assessed with a pro forma asking information about their habit and the depression, anxiety, and stress scale. Statistical analysis was done using t-test, Chi-square test, and Mann- Whitney U-test. Reasons for starting to play Pokemon Go included liking the concept (n = 39), peer pressure (n = 8), and free availability (n = 3). Wandering outside their residence alone until way after dark to play the game was reported by 27 players, and six admitted to stopping in the middle of a road to catch a rare pokemon. Twenty-eight players admitted that the game had adversely affected their behavior. Twenty players play much longer than they originally planned, whereas 22 lost track of time while playing the game. The players were under significantly more stress, anxiety, and depression compared to nonplayers. Regular playing of Pokemon Go results in adverse consequences including exposure to dangerous situations, stress, anxiety, and depression.


Comparison of Immunoassays for Measuring Serum Levels of Golimumab and Antibodies Against Golimumab in Ulcerative Colitis: A Retrospective Observational Study.
Golimumab is a monoclonal anti-tumor necrosis factor alpha antibody, which is used in ulcerative colitis with an exposure-response relationship. The goal of this study was to compare results obtained with different immunoassays (golimumab and antigolimumab antibodies trough levels). This study was based on samples from 78 ulcerative colitis patients on golimumab treatment. Golimumab was quantified by either an anti-IgG detection antibody (Theradiag, Marne la Vallée, France) or an antibody directed against golimumab (Sanquin, Amsterdam, The Netherlands, KU Leuven, Leuven, Belgium, and Janssen R&D, San Diego, CA). Bridging drug-sensitive enzyme-linked immunosorbent assays (Theradiag, Janssen R&D, and KU Leuven), a bridging drug-tolerant enzyme-linked immunosorbent assay (Janssen R&D), and a radioimmunoassay (Sanquin) were used to quantify antidrug antibody. Median serum golimumab levels were 4.5, 3.5, 4.9, and 2.4 mcg/mL with Theradiag, Sanquin, KU Leuven, and Janssen R&D assay, respectively (P < 0.05). Correlation coefficients between assays ranged from 0.9 to 0.97. When using the KU Leuven and Janssen R&D assays, 86% of samples were in the same quartile of distribution of values, and for Sanquin and Janssen R&D assays, this overlap was 80%. The concordance observed for the other pairs was 83% (Sanquin/KU Leuven R&D), 71% (Theradiag/KU Leuven), and 68% (Theradiag/Janssen R&D and Theradiag/Sanquin). The specificity of assays for golimumab was demonstrated. Antidrug antibodies were detected in 28.2% of the samples with the Janssen R&D drug-tolerant assay and in the same 2 patients by the 3 other assays. Performances of these immunoassays were similar in terms of quality, but differences in the quantitative results point to the importance of using the same assay consistently to monitor a patient's treatment.


A pH-dependent charge reversal peptide for cancer targeting.
Naturally occurring cationic antimicrobial peptides exhibit not only antimicrobial activity, but also anticancer activity and are expected to be new weapons in cancer treatment. The selectivity for cancer cells over normal cells is at least partly due to the more negative surface of cancer cells. A lower pH in tumor tissue (pH 6.2-6.9) than that in normal tissues (pH 7.3-7.4) has also been utilized to develop anticancer agents. However, cytotoxicity against normal cells at physiological pH is often an issue. Furthermore, acidic regions can be found in some normal tissues such as the kidneys. Therefore, existing approaches to cancer targeting are not fully satisfactory. In this study, we designed a peptide, HE (GIHHWLHSAHEFGEHFVHHIMNS-amide), with a charge that reverses from -1.5 at pH 7.4 to +6 at pH 5.5 for cancer targeting at low pH based on the antimicrobial peptide magainin 2 by introducing 6 His, an additional Glu, and an amidated terminal. HE interacted with cancer-mimicking negatively charged liposomes in a pH-dependent fashion with a midpoint with a pH of 6.5 just above the membrane surface. The peptide killed human renal adenocarcinoma ACHN cells at pH 6.0, but not at pH 7.4, and was nontoxic against human normal glomerular mesangial cells even at this low pH. Thus, the novel peptide may be a promising lead peptide for cancer therapy, although this derivatization resulted in weakened cytotoxicity.


Effect of troglitazone on vascular and glucose metabolic actions of insulin in high-sucrose-fed rats.
In rats, diets high in simple sugar induce insulin resistance and alter vascular reactivity. The present study was designed to evaluate the effects of 5 weeks treatment with troglitazone on insulin sensitivity, regional hemodynamics, and vascular responses to insulin in chow-fed and high-sucrose-fed rats. Male rats were randomly divided in 4 groups to receive a regular chow diet in the absence (group 1) or presence of troglitazone (0.2% in food; group 2), or a sucrose-enriched diet in the absence (group 3) or presence of troglitazone (group 4) for 5 weeks. The rats were instrumented with Doppler flow probes and intravascular catheters to determine blood pressure, heart rate, and regional blood flows. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Glucose transport activity was examined in isolated muscles. Sucrose feeding was found to induce insulin resistance and to impair the insulin-mediated skeletal muscle vasodilation. Treatment with troglitazone was found to increase whole-body insulin sensitivity in sucrose- and chow-fed rats, but had no effect on skeletal muscle glucose transport activity measured in isolated muscles from both dietary groups. Changes in regional hemodynamics were observed in both dietary cohorts treated with troglitazone, and the hindquarter vasoconstrictor response to insulin noted in sucrose-fed rats was abolished by the treatment. The vascular effects of troglitazone, and its insulin-related attenuating effects on contractile tone, could have contributed, in part, to improve insulin action on peripheral glucose disposal, presumably by improving blood flow distribution and glucose delivery.


Evidence-based medicine comes of age in pediatric cardiology.
Outcomes have improved significantly in pediatric cardiovascular disease in recent decades. The challenge now is to sustain these advances through innovative clinical trials, fundamental molecular investigations, genetics and genomics, and outreach to families, emphasizing the importance of participating in research. We describe several such efforts and provide a vision of the future for pediatric cardiovascular research.


Health-Related Quality of Life of Patients with Hidradenitis Suppurativa Measured with the 15D Instrument and Comparison with the General Population and Patients with Psoriasis.
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease significantly impacting health-related quality of life (HRQoL). We measured the HRQoL of Finnish HS patients and compared it with that of the general population and psoriasis patients. Twenty-six diagnosed HS patients completed the 15D HRQoL questionnaire (15D), the Dermatology Life Quality Index (DLQI), and the Beck Depression Inventory-21 (BDI-21). The correlation between the results of these instruments was analyzed and the 15D results were compared with an age-standardized general population and psoriasis patients. Compared with an age-standardized general population, HS patients scored statistically significantly worse on several 15D dimensions. A statistically significant difference compared to psoriasis patients was detected on the sexual activity dimension. Even though not statistically significant, the observed mean values of the remaining dimensions suggest that clinically important differences may exist. The 15D score negatively correlated with the DLQI score (r = -0.492; p = 0.011) and the BDI-21 score (r = -0.592; p = 0.001). HS is a serious condition, with an impact at least comparable to that of psoriasis. This study shows that the 15D is a feasible tool for examining HRQoL in HS patients.


Sex differences in the mouse photothrombotic stroke model investigated with X-ray fluorescence microscopy and Fourier transform infrared spectroscopic imaging.
Stroke is a leading cause of death and disability around the world. To date, the majority of pre-clinical research has been performed using male lab animals and results are commonly generalized to both sexes. In clinical stoke cases females have a higher incidence of ischemic stroke and poorer outcomes, compared to males. Best practices for improving translatability of findings for stroke, encourage the use of both sexes in studies. Since estrogen and progesterone have recognized neuroprotective effects, it is important to compare the size, severity and biochemical composition of the brain tissue following stroke in female and male animal models. In this study a photothrombotic focal stroke was induced in male and female mice. Vaginal secretions were collected twice daily to track the stage of estrous. Mice were euthanized at 24 h post-stroke. Histological staining, Fourier transform infrared imaging and X-ray fluorescence imaging were performed to better define the size and metabolic markers in the infarct core and surrounding penumbra. Our results show while the female mice had a significantly lower body mass than males, the cross-sectional area of the brain and the size of infarct and penumbra were not significantly different between the groups. In addition to the general expected sex-linked differences of altered NADH levels between males and females, estrus females had significantly elevated glycogen in the penumbra compared with males and total phosphorus levels were noted to be higher in the penumbra of estrus females. Elevated glycogen reserves in the tissue bordering the infarct core in females may present alternatives for improved functional recovery in females in the early post-stroke phase.


Effects of aminopentol on in utero development in rats.
Aminopentol (AP1), the backbone and main hydrolysis product of the mycotoxin fumonisin B1 (FB1), is present in corn-based foods which are consumed daily as a substantial part of the diet in some areas of the world. The toxicity of FB1 has been attributed to altered sphingolipid metabolism, but the toxicity of AP1 is less certain. Epidemiological correlations and in vitro studies have suggested that AP1 can increase neural tube defects (NTDs), but no in vivo developmental study of AP1 was done prior to this study. AP1 was given once daily to rats by gavage on gestation days (GD) 3-16 at doses of 0, 15, 30, 60, or 120 mg/kg. Reproductive and developmental parameters were measured at GD 17, one day after the last dose, and on GD 20. In addition, on GD 17, maternal and fetal tissues were analyzed for sphingolipid content. AP1 reduced dam body weight gain, but was less toxic than FB1. AP1 was not teratogenic, did not affect tissue sphingolipid ratios, did not alter reproduction or development of fetuses, and produced no dose-related histopathological effects in dams.


International survey of antibiotic dosing and monitoring in adult intensive care units.
In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time. A cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing, administration and monitoring of vancomycin, piperacillin/tazobactam, meropenem and aminoglycosides. A total of 538 respondents (71% physicians and 29% pharmacists) from 409 hospitals in 45 countries completed the survey. Vancomycin was mostly administered as an intermittent infusion, and loading doses were used by 74% of respondents with 25 mg/kg and 20 mg/kg the most favoured doses for intermittent and continuous infusions, respectively. Piperacillin/tazobactam and meropenem were most frequently administered as an extended infusion (42% and 51%, respectively). Therapeutic drug monitoring was undertaken by 90%, 82%, 43%, and 39% of respondents for vancomycin, aminoglycosides, piperacillin/tazobactam, and meropenem, respectively, and was more frequently performed in high-income countries. Respondents rarely used dosing software to guide therapy in clinical practice and was most frequently used with vancomycin (11%). We observed numerous changes in practice since the ADMIN-ICU 2015 survey was conducted. Beta-lactams are more commonly administered as extended infusions, and therapeutic drug monitoring use has increased, which align with emerging evidence.


Fungal spoilage of bottled mineral water.
The occurrence of filamentous fungi together with bacteriological parameters was assessed in 126 samples of still bottled mineral water of eight different commercial brands in Argentina. In spoiled samples with visible mycelium growth, the most frequently isolated fungal species were Penicillium citrinum, P. glabrum, other Penicillium species, Cladosporium cladosporioides and Alternaria alternata. In unspoiled samples, the genera found were Penicillium, Cladosporium, Rhizopus, Aspergillus and Phoma. Only three of the 126 samples failed to meet the required microbiological standards because they were found to contain faecal streptococci.


Physical activity in pregnant women with Class III obesity: A qualitative exploration of attitudes and behaviours.
To explore the barriers and facilitators to physical activity and lifestyle interventions in pregnant women with Class III obesity (body mass index >40 kg/m(2)). Qualitative study using in-depth, semi-structure interviews framed by the Theory of Planned Behaviour. Semi-structured, in-depth interviews were conducted using a topic guide. Data analysis was undertaken using a Framework Approach and was informed by the theory of planned behaviour. Recruitment and analysis continued until data saturation was reached. Participants were recruited from an antenatal clinic for women with Class III obesity. Pregnant women (n=13) with Class III obesity. Three major themes emerged from the data analysis: having a healthy lifestyle awareness, complex barriers to lifestyle changes and having personalised solutions to promote healthy lifestyle. Women were aware of the benefits of physical activity during pregnancy but had complex barriers to engaging with activity. future lifestyle interventions for women with Class III in pregnancy should take into account individual, societal and support barriers towards weight management and lifestyle choices in pregnancy. Programs that provide personalised support which are sensitive to the specific physical and psychological needs of women with Class III obesity which focus on the benefits and safety of physical activity for both mother and baby may be more likely to be successful. Further research is needed to explore the feasibility and acceptability of tailored programs.


Isolation of a subclonal cell line of PC12 transfected with dexamethasone-regulated ras oncogene: morphological differentiation, biochemical properties, and tumorigenicity.
We have isolated and characterized a new subclonal cell line designated as MR31, which was obtained by transfection of PC12 cells with a glucocorticoid-regulated ras oncogene. The mRNA derived from the c-Ha-ras gene was proved to be expressed on exposure of the MR31 cells to dexamethasone, the highest value being attained at 8 h. MR31 cells rapidly extended neurite-like processes within 24 h in response to dexamethasone as well as nerve growth factor (NGF). The time of onset of neurite outgrowth induced by dexamethasone corresponded to the time when the highest ras mRNA level was observed. The catecholamine content of MR31 cells was found to be twice that of PC12 cells. A time course study on the effects of dexamethasone or NGF on cells showed that the former caused an increase in dopamine, a major catecholamine, to twofold the control level at 48 h after the treatment, while the latter caused a decrease in the dopamine level. These effects on catecholamines were almost the same in MR31 and PC12 cells. The acetylcholinesterase activity of MR31 cells was enhanced by both dexamethasone and NGF, whereas that of PC12 cells was enhanced by NGF, but not by dexamethasone. The changes in acetylcholinesterase activity were correlated with neurite outgrowth. Electron-microscopically, MR31 cells were not different from PC12 cells. MR31 cells exhibited extremely decreased tumorigenicity as compared with PC12 cells. The morphological and biochemical properties of MR31 cells remained constant, even after repeated passages.(ABSTRACT TRUNCATED AT 250 WORDS)


Physical activity after revision knee arthroplasty including return to sport and work: a systematic review and meta-analysis including GRADE.
The number of primary knee arthroplasties (KAs) performed annually is rising, especially among active, working age patients. Consequently, revision KA is also increasingly performed. Our aim was to systematically review the extent to which patients were physically active following revision KA, and the rate and timing of return to sport and work. A search was conducted in the databases Medline and Embase until February 24th, 2023. Studies describing patients with revision total knee arthroplasty (rTKA) or revision unicondylar knee arthroplasty (rUKA), with outcomes regarding physical activity or return to sport (RTS) or work (RTW) were included. Quality of studies was assessed using the Newcastle-Ottawa scale, meta-analyses were performed using RevMan 5.4 and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Of the 4,314 articles screened, 22 studies were included describing 2,462 rTKA patients (no rUKA), 42% were male with a mean age of 67 years (range 24 - 95). No studies reported objective physical activity measurements. Twenty-two studies reported patient reported outcome measures (PROMs). The PROMs that were pooled on a scale from zero to ten were the UCLA Activity Score, the Tegner Activity Level Scale, the Lower-Extremity Activity Scale, Devane Activity Score, and physical activity related subscales of the Knee injury and Osteoarthritis Outcome Score. The retrospective studies of moderate quality showed a statistically significant postoperative improvement of 1.7 points (MD = 1.71, 95% CI 1.48 - 1.94 (p < 0.0001); 14 studies, n = 1,211). For the prospective moderate-quality studies, a statistically significant postoperative increase of 0.9 points was found (MD = 0.89, 95% CI 0.48 - 1.30 (p < 0.0001); 6 studies, n = 1,027). Regarding RTS, 12% of patients participated in so-called 'non-recommended' activities (i.e., hockey, soccer, football, gymnastics, jogging, singles tennis, and basketball) after rTKA (1 study, n = 206). The pooled RTW was 86% (2 studies, range 18-95%, n = 234). The majority of patients self-reported an improved postoperative activity level after rTKA. Patients could maintain an active lifestyle in daily life, including sports and work. For reliable physical activity, RTS and RTW estimations, more studies are required. In terms of GRADE, the quality of evidence for the five prospective studies was rated as low. Level 3.


The high identity of the Trypanosoma cruzi Group-I of trans-sialidases points them as promising vaccine immunogens.
Trans-sialidase (TS) superfamily of proteins comprises eight subgroups, being the proteins of Group-I (TS-GI) promising immunogens in vaccine approaches against Trypanosoma cruzi. Strikingly, TS-GI antigenic variability among parasite lineages and their influence on vaccine development has not been previously analyzed. Here, a search in GenBank detects 49 TS-GI indexed sequences, whereas the main infecting human different parasite discrete typing units (DTU) are represented. In silico comparison among these sequences indicate that they share an identity above 92%. Moreover, the antigenic regions (T-cell and B-cell epitopes) are conserved in most sequences or present amino acid substitutions that scarcely may alter the antigenicity. Additionally, since the generic term TS is usually used to refer to different immunogens of this broad family, a further in silico analysis of the TS-GI-derived fragments tested in preclinical vaccines was done to determine the coverage and identity among them, showing that overall amino acid identity of vaccine immunogens is high, but the segment coverage varies widely. Accordingly, strong H-2K, H-2I, and B-cell epitopes are dissimilarly represented among vaccine TS-derived fragments depending on the extension of the TG-GI sequence used. Moreover, bioinformatic analysis detected a set of 150 T-cell strong epitopes among the DTU-indexed sequences that strongly bind human HLA-I supertypes. In all currently reported experimental vaccines based on TS-GI fragments, mapping these 150 epitopes showed that they are moderately represented. However, despite vaccine epitopes do not present all the substitutions observed in the DTUs, these regions of the proteins are equally recognized by the same HLAs. Interestingly, the predictions regarding global and South American population coverage estimated in these 150 epitopes are similar to the estimations in experimental vaccines when the complete sequence of TS-GI is used as an antigen. In silico prediction also shows that a number of these MHC-I restricted T-cell strong epitopes could be also cross-recognized by HLA-I supertypes and H-2Kb or H-2Kd backgrounds, indicating that these mice may be used to improve and facilitate the development of new TS-based vaccines and suggesting an immunogenic and protective potential in humans. Further molecular docking analyses were performed to strengthen these results. Taken together, different strategies that would cover more or eventually fully of these T-cell and also B-cell epitopes to reach a high level of coverage are considered.


Factors affecting soil microbial biomass and functional diversity with the application of organic amendments in three contrasting cropland soils during a field experiment.
The effects of soil type and organic material quality on the microbial biomass and functional diversity of cropland soils were studied in a transplant experiment in the same climate during a 1-year field experiment. Six organic materials (WS: wheat straw, CS: corn straw, WR: wheat root, CR: corn root, PM: pig manure, CM: cattle manure), and three contrasting soils (Ferralic Cambisol, Calcaric Cambisol and Luvic Phaeozem) were chosen. At two time points (at the end of the 1st and 12th months), soil microbial biomass carbon (C) and nitrogen (N) (MBC and MBN) and Biolog Ecoplate substrate use patterns were determined, and the average well color development and the microbial functional diversity indices (Shannon, Simpson and McIntosh indices) were calculated. Organic material quality explained 29.5-50.9% of the variance in MBC and MBN when compared with the minor role of soil type (1.4-9.3%) at the end of the 1st and 12th months, and C/N ratio and total N of organic material were the main parameters. Soil properties, e.g., organic C and clay content were the predominant influence on microbial functional diversity in particular at the end of the 12th month (61.8-82.8% of the variance explained). The treatments of WS and CS significantly improved the MBC and microbial functional diversity indices over the control in the three soils in both sampling periods (P < 0.05). These results suggest that the application of crop straw is a long-term effective measure to increase microbial biomass, and can further induce the changes of soil properties to regulate soil microbial community.


Electrospun strong, bioactive, and bioabsorbable silk fibroin/poly (L-lactic-acid) nanoyarns for constructing advanced nanotextile tissue scaffolds.
Bio-textiles have aroused attractive attentions in tissue engineering and regenerative medicine, and developing robust, bio-absorbable, and extracellular matrix (ECM) fibril-mimicking nanofibrous textiles is urgently required for the renewal of existing microfibrous textile-based scaffolds and grafts. In this study, an integrated electrospinning system consisting of one nanoyarn-forming unit and one hot stretching unit is reported to fabricate silk fibroin (SF)/poly (L-lactic-acid) (PLLA) nanofibrous yarns (nanoyarns). The hot stretching process is demonstrated to significantly improve the fiber alignment, crystallinity, and mechanical properties of SF/PLLA nanoyarns, compared to the unstretched controls. For instance, the fiber alignment degree of hot stretched 50/50 SF/PLLA nanoyarn has increased by 25%, and the failure strength has increased by 246.5%, compared with the corresponding un-stretched control. Increasing the SF/PLLA mass ratio is found to significantly decrease the crystallinity and mechanical properties, but notably increase the degradation rate and surface hydrophilicity of SF/PLLA nanoyarns. Different SF/PLLA nanoyarns are further meticulously interwoven with warp and weft directions to obtain several nanofibrous woven textiles. The results from in vitro cell characterization and in vivo subcutaneous implantation show that increasing the SF/PLLA mass ratio significantly improves the biological properties and effectively reduces the inflammatory response of nanoyarn-constructed textiles. Overall, this study demonstrates that our SF/PLLA nanoyarns with controllable physical, mechanical and biological performances are fantastic candidates for the designing and development of advanced nanoarchitectured textile tissue scaffolds.


Determinants of acceptance of end-of-life interventions: a comparison between withdrawing life-prolonging treatment and euthanasia in Austria.
End-of-life decisions remain a hotly debated issue in many European countries and the acceptance in the general population can act as an important anchor point in these discussions. Previous studies on determinants of the acceptance of end-of-life interventions in the general population have not systematically assessed whether determinants differ between withdrawal of life-prolonging treatment (WLPT) and euthanasia (EUT). A large, representative survey of the Austrian adult population conducted in 2014 (n = 1,971) included items on WLPT and EUT. We constructed the following categorical outcome: (1) rejection of both WLPT and EUT, (2) approval of WLPT but rejection of EUT, and (3) approval of both WLPT and EUT. The influence of socio-demographics, personal experiences, and religious and socio-cultural orientations on the three levels of approval were assessed via multinomial logistic regression analysis. Higher education and stronger socio-cultural liberal orientations increased the likelihood of approving both WLPT and EUT; personal experience with end-of-life care increased only the likelihood of approval of WLPT; and religiosity decreased approval of EUT only. This study found evidence for both shared (education, liberalism) and different (religiosity, care experiences) determinants for the acceptance of WLPT and EUT.


Scaling up antiretroviral treatment services in Karnataka, India: impact on CD4 counts of HIV-infected people.
Twelve antiretroviral treatment centres under National AIDS Control Programme (NACP), Karnataka State, India. For the period 2004-2011, to describe the trends in the numbers of people living with HIV (PLHIV) registered for care and their median baseline CD4 counts, disaggregated by age and sex. Descriptive study involving analysis of routinely captured data (year of registration, age, sex, baseline CD4 count) under NACP. 34,882 (97% of total eligible) PLHIV were included in analysis. The number registered for care has increased by over 12 times during 2004-11; with increasing numbers among females. The median baseline CD4 cell count rose from 125 in 2004 to 235 in 2011--the increase was greater among females as compared to males. However, about two-thirds still presented at CD4 cell counts less than 350. We found an increasing trend of median CD4 counts among PLHIV presenting to ART centres in Karnataka, an indicator of enhanced and early access to HIV care. Equal proportion of females and higher baseline CD4 counts among them allays any fear of differential access by gender. Despite this relative success, a substantial proportion still presented at low CD4 cell counts indicating possibly delayed HIV diagnosis and delayed linkage to HIV care. Universal HIV testing at health care facilities and strengthening early access to care are required to bridge the gap.


Advances in MR spectroscopy of the prostate.
Commercial MR imaging/magnetic resonance spectroscopic imaging (MRSI) packages for staging prostate cancer on 1.5-T MR scanners are now available. The technology is becoming mature enough to begin assessing its clinical utility in selecting, planning, and following prostate cancer therapy. Before therapy, 1.5-T MR imaging/MRSI has the potential to improve the local evaluation of prostate cancer presence and volume and has a significant incremental benefit in the prediction of pathologic stage when added to clinical nomograms. After therapy, two metabolic biomarkers of effective and ineffective therapy have been identified and are being validated with 10-year outcomes. Accuracy can be improved by performing MR imaging/MRSI at higher magnetic field strengths, using more sensitive hyperpolarized (13)C MRSI techniques and through the addition of other functional MR techniques.


A qualitative study on people with opioid use disorders' perspectives on smoking and smoking cessation interventions.
Smoking-related diseases are major contributors to disability and shorter life expectancy among opioid-dependent patients. Smoking prevalence is considerably higher for opioid-dependent persons than among the general population, and only a minority quit smoking in treatment settings. Studies show that pharmacological smoking cessation interventions have modest success rates. This study aimed to investigate patients' receiving opioid agonist therapy perspectives on factors affecting behavior and decisions related to smoking cessation, and their experiences with smoking cessation. This is a qualitative study using semi-structured individual interviews. The participants were asked, among others, to elaborate on the participants' thoughts about smoking, previous attempts to quit tobacco use, and what could prompt a smoking cessation attempt. We analyzed the transcripts with systematic text condensation. The Standards for Reporting Qualitative Research and the Consolidated Criteria for Reporting Qualitative Research guidelines were followed. Opioid-dependent patients receiving opioid agonist therapy in outpatient clinics were invited to participate using a purposive sampling method. In total, fourteen individuals participated in this study. We identified six themes which were: (1) reflections on how smoking affected decisions, (2) smoking and its impact on physical and mental health, (3) the economy as a motivator to stop smoking, (4) emotions, desires, and habits related to smoking, (5) knowledge of smoking, smoking cessation, and quit attempts, and (6) social factors influencing the participants' choices and activities. The participants were well informed about the consequences of smoking and had some knowledge and experience in quitting. The participants' pulmonary health was an important motivational factor for change. Withdrawal symptoms, anxiety, and fear of using other substances discouraged several from attempting to quit smoking. In contrast, social support from partners and access to meaningful activities were considered important factors for success. Few reported being offered help from health professionals to make a smoking cessation attempt. Experiencing social support, being encouraged to quit smoking, and patients' concerns for their physical health were important reasons for wanting to quit smoking. Smoking cessation interventions based on patient preferences and on the behavior change wheel may enable a higher success rate among patients receiving opioid agonist therapy.


The Association Between Urinary Cadmium Levels and Dietary Habits with Risk of Gastrointestinal Cancer in Tabriz, Northwest of Iran.
Cadmium (Cd) is a widespread toxic heavy metal and has long biological half-life. It has potential carcinogenic effects on multiple organ systems of human. However, no studies have evaluated the adverse effects of cadmium on incidence of cancer in gastrointestinal tract. The aim of this study was to investigate the association between urine cadmium (U-Cd) levels and risk of gastrointestinal cancer. This descriptive study was accomplished on 111 GI cancer patients as cases and 111 healthy people as control subjects from January to October in Tabriz, northwest Iran, during 2013. Cadmium in urine samples was measured by graphite furnace atomic absorption spectrophotometer (GFAAS). GI cancer patients had higher urine cadmium levels in comparison to healthy individuals (p < 0.05). The multivariate regression model manifested a significant association between the U-Cd concentrations and the risk of GI cancer (odds ratio (OR) = 1.70, 95 % CI = 1.35-2.20). Cases were 70 % more than controls at risk of cancer incidence. Our data indicates an association between U-Cd levels and GI cancer risk.


NRF2 and FXR dual signaling pathways cooperatively regulate the effects of oleanolic acid on cholestatic liver injury.
Previous studies have shown that the anti-cholestatic effect of oleanolic acid (OA) is associated with FXR and NRF2. However, how the two signaling pathways cooperate to regulate the anti-cholestatic effect of OA remains unclear. This study aimed to further demonstrate the effect of OA on alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury and the interaction mechanism between NRF2 and FXR signaling pathways in maintaining bile acid homeostasis. Gene knockout animals and cell models, metabolomics analysis, and co-immunoprecipitation were used to investigate the mechanism of OA against cholestatic liver injury. The effect of OA against ANIT-induced liver injury in rats was dramatically reduced after Nrf2 gene knockdown. With the silencing of Fxr, the hepatoprotective effect of OA was weakened, but it still effectively alleviated cholestatic liver injury in rats. In L02 cells, OA can up-regulate the levels of NRF2, FXR, BSEP and UGT1A1, and reduce the expression of CYP7A1. Silencing of NRF2 or FXR significantly attenuated the protective effect of OA on ANIT-induced L02 cell injury and its regulation on downstream target genes, and the influence of NRF2 gene silencing on OA appeared to be greater. The NRF2 activator sulforaphane, and the FXR activator GW4064 both remarkably promoted NRF2 binding to P300 and FXR to RXRα, but reduced β-catenin binding to P300 and β-catenin binding to FXR. The effect of OA on cholestatic liver injury is closely related to the simultaneous activation of NRF2 and FXR dual signaling pathways, in which NRF2 signaling pathway plays a more important role. The dual signaling pathways of NRF2 and FXR cooperatively regulate bile acid metabolic homeostasis through the interaction mechanism with β-catenin/P300.


Development and hatching mechanism of Fasciola eggs, light and scanning electron microscopic studies.
Both light microscopy and scanning electron microscopy were used in the description. There were variable measurements of eggs from the same fluke and there was no relationship between the size of the fluke and size of eggs. Light microscopy revealed that the operculum has different shapes in Fasciola gigantica and F. hepatica. Under normal laboratory conditions of temperature (26 ± 1 °C), miracidia of F. gigantica developed within 12-16 days period, but those of F. hepatica developed within a period of 13-15 days. The miracidia of F. gigantica measured 110 × 70 μm and that of F. hepatica measured 136 × 74 μm. The life span of the miracidium in F. gigantica ranged between 9 and 12 h, while in F. hepatica the life span did not exceed 10 h. Miracidial epidermal plates in miracidium of F. gigantica were found to be 20 plates arranged in four tiers of six, four, six and four. Hatching process was recorded using scanning electron microscope, and it indicated partially opened operculum.


Computerised measures of electro-oculographic activity during sleep.
Since electro-oculographic (EOG) activity during human sleep appears to be of medical diagnostic and prognostic value, the vast amount of EOG data representative of even a single night's sleep warrants the development of automated pattern recognition and information extraction techniques. Such a technique for the analysis of sleep EOG rapid eye movement (REM) is presented in which the time of occurrence, area, height, duration and binocular symphrony for each REM are measured. This automated technique for sleep EOG analysis is currently used in the investigation of periodicities and values of REM parameters for normal subjects and in the differential diagnosis of affective disorders.


Temperature-sensitive membrane association of pp60src in tsNY68-infected cells correlates with increased tyrosine phosphorylation of membrane-associated proteins.
Incubation of membrane vesicles from normal and Rous sarcoma virus-transformed chick embryo fibroblasts (CEF) with [gamma-32P]ATP resulted in the phosphorylation of a large number of proteins. The major differences observed between the membrane vesicles of untransformed and transformed cells were: (1) a 5- to 10-fold increase in the proportion of labeled phosphotyrosine in transformed vesicles and (2) the phosphorylation of pp60src in vesicles from transformed cells. Of the many proteins labeled in vitro, only pp60src was immunoprecipitated by TBR serum. Phosphorylation of the immunoprecipitated pp60src occurred on tyrosine in the 26-kDa carboxy-terminal Staphylococcus aureus V8 protease fragment. pp60src was not phosphorylated in vitro in membrane vesicles prepared from tsNY68-infected cells grown at the nonpermissive temperature. The proportion of labeled phosphotyrosine in membrane proteins from tsNY68-infected cells grown at the nonpermissive temperature was only slightly increased relative to that observed in membranes prepared from normal cells. Subcellular fractionation indicated that while pp60src was membrane associated in tsNY68-infected cells grown at the permissive temperature, pp60src was chiefly soluble in tsNY68-infected cells grown at the nonpermissive temperature. Temperature-sensitive membrane association of pp60src in tsNY68-infected cells was also observed by indirect immunofluorescence microscopy. When membranes were prepared from tsNY68-infected cells that had been downshifted from the nonpermissive to the permissive temperature, the reappearance of in vitro phosphorylated pp60src and the increase in the proportion of labeled phosphotyrosine in membrane vesicles correlated with the kinetics of src immune complex kinase reactivation and membrane association of pp60src.


Evaluation of Retinal Nerve Fiber Layer Thickness and Ganglion Cell Complex Progression Rates in Healthy, Ocular Hypertensive, and Glaucoma Eyes With the Avanti RTVue-XR Optical Coherence Tomograph Based on 5-Year Follow-up.
To determine retinal nerve fiber layer thickness (RNFLT) and ganglion cell complex (GCC) progression rates for healthy eyes and undertreatment ocular hypertensive (OHT) and glaucoma eyes with the Avanti RTVue-XR optical coherence tomography. Seventeen healthy subjects (34 eyes), 17 medically treated OHT patients (34 eyes), and 67 medically treated glaucoma patients (122 eyes) were imaged prospectively at 6-month intervals (median follow-up 5.3 y, 11 visits). A minimal negative correlation between baseline RNFLT and RNFLT progression was found in the glaucoma group (r=-0.1708, P=0.0493). In the other groups no correlation between baseline RNFLT or GCC and RNFLT or GCC progression was found, respectively. The mean±SD of the rate of change was -0.33±0.51, -0.44±0.62, and -0.69±0.93 μm/y for average RNFLT, and -0.53±0.36, -0.54±0.52, and -0.80±0.78 for average GCC, for the normal, OHT, and glaucoma eyes, respectively (P>0.05 for all between-group comparisons). In the normal group the highest progression rate was -1.52 μm/y for average RNFLT and -1.28 μm/y for average GCC. Despite maximal medical treatment, progression in the glaucoma group exceeded the highest progression rate of the normal group in 18 eyes (14.8%) for average RNFLT and 24 eyes (19.7%) for average GCC. We determined progression rates for untreated healthy and under treatment OHT and glaucoma eyes with the Avanti RTVue-XR optical coherence tomography. We found that an average RNFLT progression rate faster than -1.5 μm/y, and an average GCC progression rate faster than -1.3 μm/y are strongly suggestive for uncontrolled glaucomatous progression. Detection of uncontrolled structural progression with trend analysis may assist the early detection of fast progressors.


Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-beta1.
Transforming growth factor beta1 (TGF-beta1) is a cardinal cytokine in the pathogenesis of airway remodeling, and promotes epithelial-to-mesenchymal transition (EMT). As a molecular interaction between TGF-beta1 and Jun N-terminal kinase (JNK) has been demonstrated, the goal of this study was to elucidate whether JNK plays a role in TGF-beta1-induced EMT. Primary cultures of mouse tracheal epithelial cells (MTEC) from wild-type, JNK1-/- or JNK2-/- mice were comparatively evaluated for their ability to undergo EMT in response to TGF-beta1. Wild-type MTEC exposed to TGF-beta1 demonstrated a prominent induction of mesenchymal mediators and a loss of epithelial markers, in conjunction with a loss of trans-epithelial resistance (TER). Significantly, TGF-beta1-mediated EMT was markedly blunted in epithelial cells lacking JNK1, while JNK2-/- MTEC underwent EMT in response to TGF-beta1 in a similar way to wild-type cells. Although Smad2/3 phosphorylation and nuclear localization of Smad4 were similar in JNK1-/- MTEC in response to TGF-beta1, Smad DNA-binding activity was diminished. Gene expression profiling demonstrated a global suppression of TGF-beta1-modulated genes, including regulators of EMT in JNK1-/- MTEC, in comparison with wild-type cells. In aggregate, these results illuminate the novel role of airway epithelial-dependent JNK1 activation in EMT.


Leishmania donovani HslV does not interact stably with HslU proteins.
Genes for HslVU-type peptidases are found in bacteria and in a few select Eukaryota, among those such important pathogens as Plasmodium spp. and Leishmania spp. In this study, we performed replacements of all three HslV/HslU gene homologues and found one of those, HslV, to be essential for Leishmania donovani viability. The Leishmania HslV gene can also partially relieve the thermosensitive phenotype of a combined HslVU/Lon/ClpXP knockout mutant of Escherichia coli, indicating a conserved function. However, we found that the role and function of the two Leishmania HslU genes has diverged since neither of those interacts stably with HslV. The latter forms a dodecameric complex by itself and shows a punctate distribution. We conclude that whilst the basic function of HslV may be conserved in Leishmania, its organisation and interaction with its canonical complex partner HslU is not. Nevertheless, given the absence of HslV from the proteome of mammals and its essential role in Leishmania viability, HslV is a promising target for intervention.


Comparison between spoligotyping and IS6110 restriction fragment length polymorphisms in molecular genotyping analysis of Mycobacterium tuberculosis strains.
Spoligotyping was compared with RFLP fingerprinting analysis in the identification of Mycobacterium tuberculosis strains. Spoligotyping sensitivity was 97.6% with a specificity of 47%. The global probability for two strains clustered with spoligotyping to be clustered also with RFLP analysis was 33%; the probability for two strains clustered with RFLP analysis to be clustered also with spoligotyping analysis was 95%. However, comparing the two methods in five outbreak episodes, full concordance was evidenced between spoligotyping and RFLP. Moreover, we evaluated the presence of our 17 largest spoligotyping clusters in spoligotyping databases from Caribbean countries, London and Cuba. Only five out of 17 patterns were present in all the cohorts. The conditional probability comparing spoligotyping and RFLP methods related to these patterns resulted in very low concordance (range from 2 to 38%). In conclusion, we confirm that spoligotyping when used alone overestimates the number of recent transmission and does not represent a suitable method for wide clinical practice application. However, it allows to get a first good picture of strain identity in a new setting and in more localized or confined settings, the probability of reaching the same result compared to RFLP was 100% confirming the usefulness of spoligotyping in the management of epidemic events, especially in hospitals, prisons and close communities.


Contributions of Morphological Skill to Children's Essay Writing.
Morphological skills have previously been found to reliably predict reading skill, including word reading, vocabulary, and comprehension. However, less is known about how morphological skills might contribute to writing skill, aside from its well-documented role in the development of spelling. This correlational study examines whether morphological skill, as measured by a sentence generation task tapping both derivational morphology and meta-syntactic skills, predicts performance on a standardized essay writing task for fifth- and eighth-grade U.S. students (N = 233), after controlling for grade level, comprehension, and writing fluency. Multilevel analyses indicated that morphological skill and writing fluency were each uniquely predictive of essay quality, and this finding was consistent regardless of whether accurate spelling was required in the morphological task. Our results suggest that morphological skills play an important role in writing, as has been previously documented in reading and spelling.


Chest wall deformity in patients with repaired esophageal atresia.
Chest wall deformities developed after thoracotomy for esophageal atresia, in 77 of 232 patients (33%) who did not have a congenital vertebral anomaly. Anterior chest wall asymmetry was present in 47, scoliosis in 18 and a combination of both in 12 patients. Scoliosis was convex away from the incision in two thirds of those affected. Anterior chest wall deformity was more common in patients greater than 25 years of age, and scoliosis was more common in patients who had had multiple thoracotomies. Breast surgery to minimize inequality was required in three female patients, and spinal surgery in one patient. Twenty-two of 53 patients with a congenital vertebral anomaly developed scoliosis, eight of whom required surgery. The scoliosis was probably the result of the vertebral anomaly in these patients, who are particularly at risk for progressive deformity.


A novel insight into the key gene signature associated with the immune landscape in the progression of sarcopenia.
Sarcopenia is an age-related skeletal muscle disorder that causes falls, disability and death in the elderly, but its exact mechanism remains unknown. In this study, we merged three GEO datasets into the expression profiles of 118 samples and screened 22 differentially expressed genes (DEGs) as candidate genes. Pathway analysis demonstrated that the functional enrichment of DEGs is mainly in the cellular response to insulin stimulus, PPAR signaling pathway and other metabolism-related pathways. Then, we identified six key genes by machine learning, which were confirmed to be closely associated with sarcopenia by bioinformatics analysis. It was experimentally verified that SCD1 exhibits the most substantial alterations in the progression of sarcopenia with disturbed lipid metabolism and myosteatosis. In addition, the immune microenvironment of sarcopenia was found to be affected by these key genes, with Th17 cells down-regulated and NK cells up-regulated. Sarcopenic patients consequently presented a more significant systemic inflammatory state with higher CAR (p = 0.028) and PAR (p = 0.018). For the first time, we identified key genes in sarcopenia with high-throughput data and demonstrated that key genes can regulate the progression of sarcopenia by affecting the immune microenvironment. Among them, SCD1 may influence lipid metabolism and myosteatosis process. Screening of key genes and analyzing of immune microenvironment provide a more accurate target for treating sarcopenia.


Delayed pleuroperitoneal leak in an otherwise uncomplicated course of peritoneal dialysis.
Pleuroperitoneal leaks are rare and normally arise as an early complication in peritoneal dialysis. This case illustrates the importance of considering pleuroperitoneal leaks as a cause for pleural effusions-even if peritoneal dialysis has been longstanding and uncomplicated. A 66-year-old male on peritoneal dialysis for 15 months presented with dyspnoea and low ultrafiltration volumes. Chest radiography revealed a large right-sided pleural effusion. Pleural fluid sampling and peritoneal scintigraphy confirmed a pleuroperitoneal leak.


Interkingdom signaling in plant-rhizomicrobiome interactions for sustainable agriculture.
The rhizosphere is a complex ecosystem around plant roots that comprises an integrated network of plant roots, the microbiome and soil. Wide spread communication between prokaryotes and eukaryotes occurs within this integrated network via a complex set of signal molecules secreted during both beneficial and harmful interactions. Intra- and inter-species communication among microbes occurs through various signal molecules that coordinate and control the behaviours of microorganisms in mixed communities. In addition, interkingdom signal exchange between plants and microbes occurs through the release of root exudates from the host plants. The diverse chemical substances released in root exudates affect the structural and physical heterogeneity of the soil. Moreover, chemical compounds released in root exudates trigger various signaling pathways in microbial populations that influence rhizosphere biology. Therefore, deciphering the language of interkingdom communication and understanding the mechanisms involved is innovative and promising approach for improving crop production in sustainable agriculture. This chapter describes briefly the shaping of the rhizomicrobiome in response to released root exudates. Moreover, predicting and controlling the microbiome structure and its function in the rhizosphere by understanding of rhizomicrobiome communication through different secreted compounds will allow us to better harness beneficial plant-microbe interactions. The recent progress in understanding interkingdom communication and interactions between plants and microbes is discussed in relation to plant growth, gene expression, nutrient uptake and resistance to pests and diseases along with mitigation of abiotic stresses in plants to improve plant ecosystem productivity for sustainable agriculture.


Enhanced methane production via repeated batch bioaugmentation pattern of enriched microbial consortia.
Using batch and repeated batch cultivations, this study investigated the effects of bioaugmentation with enriched microbial consortia (named as EMC) on methane production from effluents of hydrogen-producing stage of potato slurry, as well as on the indigenous bacterial community. The results demonstrated that the improved methane production and shift of the indigenous bacterial community structure were dependent on the EMC/sludge ratio and bioaugmentation patterns. The methane yield and production rate in repeated batch bioaugmentation pattern of EMC were, respectively, average 15% and 10% higher than in one-time bioaugmentation pattern of EMC. DNA-sequencing approach showed that the enhanced methane production in the repeated batch bioaugmentation pattern of EMC mainly resulted from the enriched iron-reducing bacteria and the persistence of the introduced Syntrophomonas, which led to a rapid degradation of individual VFAs to methane. The findings contributed to understanding the correlation between the bioaugmentation of microbial consortia, community shift, and methane production.


Clinical application of pyrrole-hemoglobin adducts as a biomarker of pyrrolizidine alkaloid exposure in humans.
Pyrrolizidine alkaloids (PAs) are naturally occurring hepatotoxins widely present in hundreds of plant species and also known to contaminate many foodstuffs, such as grain, honey, and tea. The formation of pyrrole-protein adducts via metabolic activation of PAs has been suggested as a primary trigger initiating hepatotoxicity. The present study for the first time tested the suitability of pyrrole-hemoglobin adducts as a novel and specific biomarker of PA exposure in humans. The level and elimination kinetics of pyrrole-hemoglobin adducts were systematically investigated in the blood samples of 43 PA-induced liver injury (PA-ILI) patients. The results revealed significantly higher concentrations (84.50 ± 78.38 nM) and longer persistence (~ 4 months) of pyrrole-hemoglobin adducts than that (concentration: 9.53 ± 10.72 nM; persistence: ~ 2 months) of pyrrole-plasma protein adducts, our previously developed PA exposure biomarker. Our findings confirmed that pyrrole-hemoglobin adducts with higher level and longer persistence should serve as a more applicable PA exposure biomarker for future clinical diagnosis of PA-ILI in drug/herb-induced liver injury patients.


Lexiva: blood levels not lowered when taken simultaneously with Nexium.
A study suggested that the two drugs might be used together, without lowering the blood level of Lexiva. But the timing of the doses may be critical.


Exercise Intolerance After Mild Traumatic Brain Injury Occurs in All Subtypes in the Adult Population.
Thematically grouped symptom clusters are present during the acute timeline of post-mild traumatic brain injuries (mTBI), representing clinical profiles called subtypes. Exercise intolerance has not been evaluated within the subtype classifications and, because guidelines support early submaximal aerobic exercise, further knowledge is required in regard to the exercise capabilities among the concussion subtypes. This cross-sectional study (n = 78) aimed to characterize the presence of exercise intolerance within the clinical subtypes and to explore performance on the Buffalo Concussion Treadmill Test (BCTT) in the adult subacute (2-12 weeks post-injury) mTBI population. All participants were evaluated using the BCTT to determine exercise tolerance. We first used the Neurobehavioral Symptom Inventory (NSI) questionnaire to assign each participant a primary subtype(s). To further explore all five subtypes (headache, cognitive, vestibular, ocular motor, and mood), participants were assessed using a multitude of thematically grouped assessments including self-reported questionnaires, clinical tests of vestibular and ocular motor function, balance function, and computerized cognitive testing. Thirty-seven (47%) subjects were exercise tolerant and 41 (53%) were exercise intolerant. There was no difference in the distribution of primary subtypes between the exercise tolerant and exercise intolerant groups. In addition, no significant differences were found between the exercise tolerant and exercise intolerant groups on other thematically grouped subtype assessments. The exercise intolerant group had a significantly higher resting heart rate (HR), lower percentage of age-predicted maximum HR achieved, lower Borg Rate of Perceived Exertion (RPE), and could walk on the treadmill for less time (lower duration) compared with the exercise tolerant group. The current findings suggest that exercise intolerance is common and pervasive across all five mTBI subtypes. A comprehensive mTBI assessment should include evaluation for exercise intolerance regardless of the primary clustering of symptoms and across patient populations. Therefore, early referral to physical therapists, athletic trainers, or medical clinics that can perform the BCTT may be helpful to initiate appropriate exercise prescriptions for patients with mTBI.


Licensing the future: report on BioMed Central's public consultation on open data in peer-reviewed journals.
We report the outcomes of BioMed Central's public consultation on implementing open data-compliant licensing in peer-reviewed open access journals. Respondents (42) to the 2012 consultation were six to one in favor (29 in support; 5 against; 8 abstentions) of changing our authors' default open access copyright license agreement, to introduce the Creative Commons CC0 public domain waiver for data published in BioMed Central's journals. We summarize the different questions we received in response to the consultation and our responses to them - matters such as citation, plagiarism, patient privacy, and commercial use were raised. In light of the support for open data in our journals we outline our plans to implement, in September 2013, a combined Creative Commons Attribution license for published articles (papers) and Creative Commons CC0 waiver for published data.


Gender-moderated links between urgency, binge drinking, and excessive exercise.
Exercise correlates with alcohol use, but the nature of this relation and the extent to which it is maladaptive remains unclear. Urgency and motives for engaging in drinking and exercise might indicate when these behaviors are problematic. The current study examined whether urgency moderated the association between exercise motivated by weight loss and drinking. College students (N = 589, 45.7% male) completed the study during the spring of 2012. Participants completed self-report assessment measures, including frequency/quantity of alcohol consumption, exercise for weight loss, and urgency, during a single session. Negative urgency moderated the relation between exercise and alcohol consumption in men but not women; the link between excessive exercise and alcohol use was stronger for men with higher levels of urgency. Further clarification of the mechanisms underlying alcohol use and physical activity-particularly maladaptive approaches to exercise-will inform health interventions among college students.


Percutaneous endoscopic lumbar discectomy versus open lumbar microdiscectomy for treating lumbar disc herniation: Using the survival analysis.
This study compared the risk of symptomatic recurrent disc herniation and clinical outcomes of percutaneous endoscopic lumbar discectomy (PELD) versus open lumbar microdiscectomy (OLM) for lumbar disc herniation with 2 years of follow-up. We analyzed 23 patients who underwent PELD and 32 patients who underwent OLM for lumbar disc herniation. The numeric rating scale of back and leg pain, Oswestry Disability Index (ODI), and Roland-Morris Disability Questionnaire (RMDQ) were assessed before and at 12 and 24 months after the surgery. The wound pain and complications were also recorded. Survival analysis was performed to estimate the risk of symptomatic recurrent disc herniation. In the comparison of groups, the reductions in back and leg pain, ODI, and RMDQ were not significantly different at 12 and 24 months. For patients who underwent PELD, the wound pain was significant lower at the day of surgery. The survival rate of patients who were free from symptomatic recurrent disc herniation at 24 months was 0.913 in PELD and 0.875 in OLM, and the log-rank test revealed no significant difference between the two survival curves. The incidence of complication was not significantly different between groups. Both PELD and OLM are effective treatments for lumbar disc herniation because they have similar clinical outcomes. PELD provided patients with less painful wounds. The survival analysis revealed that the risk of symptomatic recurrent disc herniation in 2 years of follow-up was not different between PELD and OLM.


Enhanced Negative Thermal Expansion Induced by Simultaneous Charge Transfer and Polar-Nonpolar Transitions.
Negative thermal expansion (NTE) induced by simultaneous mechanisms, that is, charge transfer and polar-nonpolar transitions, was observed for the first time in BiNi1-xFexO3 (0.25 ≤ x ≤ 0.5). The low-temperature phase was found to have a polar structure (space group of R3c) with a Bi3+0.5(1+x)Bi5+0.5(1-x)Ni2+1-xFe3+xO3 charge distribution and short-range ordering of Bi3+ and Bi5+. The volume reduction upon heating that was induced by charge transfer between Bi5+ and Ni2+ decreased with increasing x because of the reduction in the amount of Ni2+. Simultaneous polar-nonpolar transition also contributed to NTE, and a composition-independent enhanced volume reduction of ∼2% was observed.


Solitaire® stent for endovascular coil retrieval.
Coil migration during embolization is an emergency, requiring individual solutions. A 71-year-old female patient was referred to our hospital suffering from subarachnoid hemorrhage due to a ruptured giant aneurysm of the ophthalmic segment of the right internal carotid artery (ICA). During the endovascular procedure, a coil migrated in the ICA. Coil dislocation could be treated by either retrieval or fixation. On intention to treat we retrieved the coil with the self-expanding Solitaire(®) AB stent (Ev3, Irvine, CA, USA). The Solitaire(®) stent is established to perform mechanical thrombectomy for treatment of acute stroke. This report demonstrates the Solitaire(®) stent's potential for safe and effective retrieval of dislocated coils. Other retrieval systems will be discussed.


Microsurgical research--a personal experience.
The author recounts his 38 years in microsurgical research from the early days of needle and instrument development to the first successful experimental and clinical microvascular transplants. Selected projects are discussed relating to microvascular thrombosis, vascular spasm and various experimental models in the rat, rabbit and rhesus monkey in an anecdotal fashion.


Autoantibodies against ATP4A are a feature of the abundant autoimmunity that develops in first-degree relatives of patients with type 1 diabetes.
Type 1 diabetes is associated with autoantibodies to different organs that include the gut. The objective of the study was to determine the risk of developing gastric parietal cell autoimmunity in relation to other autoimmunity in individuals with a family history of type 1 diabetes. Autoantibodies to the parietal cell autoantigen, H+ /K+ ATPase subunit A (ATP4A) was measured in 2218 first-degree relatives of patients with type 1 diabetes, who were prospectively followed from birth for a median of 14.5 years. All were also tested regularly for the development of islet autoantibodies, transglutaminase autoantibodies, and thyroid peroxidase autoantibodies. The cumulative risk to develop ATP4A autoantibodies was 8.1% (95% CI, 6.6-9.6) by age 20 years with a maximum incidence observed at age 2 years. Risk was increased in females (HR, 1.9; 95% CI, 1.3-2.8; p = 0.0004), relatives with the HLA DR4-DQ8/DR4-DQ8 genotype (HR, 3.4; 95% CI, 1.9-5.9; p < 0.0001) and in participants who also had thyroid peroxidase autoantibodies (HR, 3.7; 95% CI, 2.5-5.5; p < 0.0001). Risk for at least one of ATP4A-, islet-, transglutaminase-, or thyroid peroxidase-autoantibodies was 24.7% (95% CI, 22.6-26.7) by age 20 years and was 47.3% (95% CI, 41.3-53.3) in relatives who had an HLA DR3/DR4-DQ8, DR4-DQ8/DR4-DQ8, or DR3/DR3 genotype (p < 0.0001 vs. other genotypes). Relatives of patients with type 1 diabetes who have risk genotypes are at very high risk for the development of autoimmunity against gastric and other organs.


Yersinia enterocolitica meningitis and septicaemia in a patient with acute lymphoblastic leukaemia.
We report the first case of Yersinia enterocolitica meningitis and septicaemia during induction treatment for acute lymphoblastic leukaemia. The patient was also being treated with recombinant granulocyte colony stimulating factor and hence pursued an unusually mild clinical course.


Intra-abdominal Candida infection during acute necrotizing pancreatitis has a high prevalence and is associated with increased mortality.
To analyze the frequency of intra-abdominal Candida infection during acute necrotizing pancreatitis and to compare the outcome to patients without Candida infections. Retrospective analysis of data from 37 patients with and without Candida infection. Surgical intensive care unit (ICU) in a university hospital. Thirty-seven patients with acute necrotizing pancreatitis. Patients were subject to necrosectomy and programmed lavage. Clinical parameters contained in the Acute Physiology and Chronic Health Evaluation (APACHE) II score were monitored, as were microbiological results from the intra-abdominal primary focus and from sites of secondary infections. Body mass index, distribution of underlying diseases, length of ICU stay, number of operations, and outcome were recorded. Multivariate logistic regression analysis for mortality as the dependent variable was performed. Intra-abdominal Candida infection was observed in 13 of 37 cases and was associated with a four-fold greater mortality rate compared with intra-abdominal bacterial infection alone. Multivariate logistic regression analysis demonstrated that Candida infection contributed to mortality significantly (p < .025) and independently from APACHE II (p < .006; mortality odds ratio for the two parameters=12.5). Lack of antimycotic treatment was associated with an increase to 29.2 (p<.001) in the odds ratio. Given the impact of Candida infection on mortality to acute necrotizing pancreatitis and the apparent benefit from antimycotic chemotherapy, the data argue for an early fungicide chemotherapeutic intervention.


A case report of cutaneous infection with Mycobacterium neoaurum.
Cutaneous infection due to Mycobacterium neoaurum in immune-competent individuals had only been reported in limited cases. The point that makes our case very impressive was its cutaneous infection, and presentation in the immune-competent patient. Cutaneous infections caused by nontuberculous mycobacteria usually occur in immunocompromised hosts. We report a rare case of cutaneous infection caused by Mycobacterium neoaurum in an immune-competent patient.


[Sarcoma botryoides of the cervix uteri as cause for haemorrhages in childbed (author's transl)].
A case of a 21-year-old woman with a botryoid sarcoma of the cervix uteri, who consulted a specialist for women's diseases because of non stopping haemorrhages in childbed, is reported. Neither radical operation nor radiation nor treatment with cytostatica could arrest the extreme impetuous growth of this tumor.


Application of probability circles analysis to the construction of calibration curves for infra red spectroscopy.
A new method, based on the presentation of initial data in the form of probability circles (PC), has been developed for constructing a calibration curve, which shows a monotonic dependence with respect to the given concentration. The centre of the reference probability circle is defined by its mean value and the radius of the circle is calculated as the value of the standard deviation of the sampling considered. The comparative probability circle is defined by the same corresponding parameters but rotated, relative to the initial reference circle, by an angle, which is related to the Pearson's correlation coefficient (PCC). The two parameters of the PCC and the statistical proximity factor (PCF), which defines the positions of the centres of the circles relative to each other, can be chosen as statistical parameters for the construction of the desired calibration curve. Experiments realized with the mixture of two liquids (chloroform serves as the basic matrix) and acetone (serves as an additive) confirm the efficiency of this new analytical method and demonstrate a possible increase sensitivity for the detection of lower concentration limit by approximately one order of magnitude. This new approach, which is free from model assumptions, and having very clear geometrical meaning, can be applied for different types of spectra and has many potential applications in the construction of calibration curves for different additives embedded within different matrices.


Orientation of the guanine operon of Escherichia coli K-12 by utilizing strains containing guaB-xse and guaB-upp deletions.
Temperature induction of an Escherichia coli strains with lambda cI1857 integrated in the guaB gene has been used to produce strains containing chromosomal deletions extending into the xse and upp genes. By utilizing strains containing these deletions, it has been possible to order the genes in the guanine operon with respect to the xseA and upp genes. The order of the genes in this region is glyA-hisS-xseA-guaO-guaB-guaA-purG-upp-purC.


Gene delivery by retroviruses.
Gene delivery by retroviruses is an easy and safe tool to stably over express a gene of interest and determine its role in a cell model. The gene of interest is cloned into the multiple cloning site of a retroviral vector that also contains a packaging signal and an antibiotic resistance marker for selection. Packaging cell lines, transfected with a retroviral vector containing the gene of interest or with a control vector, produce retroviral RNA packaged into infectious, replication incompetent virus. This is a consequence of the stable integration of the viral genes necessary for particle formation and replication into the packaging cell genome. Retrovirus-containing conditioned medium from packaging cells is used to transduce target cells. After antibiotic selection, the target cells are tested for overexpression of the gene of interest and its biological effects.


Public Perception and Viewpoints of Dental Radiograph Prescriptions and Dentists' Safety Protection Practice.
The exposure of patients to ionizing radiation used in dentistry comes with a subtle risk of a stochastic effect, but there is tremendous benefit obtained from radiographic investigation for diagnosis, management, and monitoring of the treatment offered. The aim of this study was to assess the viewpoint of the population concerning the prescriptions and practices in dentistry associated with dental radiographs and the safe use of ionizing radiation in dental clinics. Validated and pretested structured self-administered questionnaires with 11 items were used. An electronic version of the questionnaire was created using Google Forms and distributed online through social media outlets. A total of 437 patients completed the questionnaire which contains questions about their demographic data and their perception of the practice of dentistry regarding hazard from dental radiographs. The collected data were analyzed statistically. Up to 88.6% of the study participants underwent dental radiography for various dental treatments. A majority of them relied on the dentist for the type of requested radiograph, 40% of them reported that dentist never explained the hazards associated with radiography. More than half of the participants (55%) never or hardly ever asked about safety measures before undergoing radiography. Most of the participants approved of radiography and never refrained. There is a spectrum of perceptions by the population. Continuous patient education is recommended to enhance awareness regarding this matter. Community perception assists in correcting wrong beliefs and ensuring improvement.


Correction to: Dubin-Johnson syndrome and intrahepatic cholestasis of pregnancy in a Sri Lankan family: a case report.
Following publication of the original article [1], the authors requested the following corrections: 1. Author 2-given name should be Dilanthi and family name Warawitage. 2. Author 6-given name should be Nalika and family name de Silva.


On the primacy of molecular processes in determining response rates under variable-ratio and variable-interval schedules.
This study focused on variables that may account for response-rate differences under variable-ratio (VR) and variable-interval (VI) schedules of reinforcement. Four rats were exposed to VR, VI, tandem VI differential-reinforcement-of-high-rate, regulated-probability-interval, and negative-feedback schedules of reinforcement that provided the same rate of reinforcement. Response rates were higher under the VR schedule than the VI schedule, and the rates on all other schedules approximated those under the VR schedule. The median reinforced interresponse time (IRT) under the VI schedule was longer than for the other schedules. Thus, differences in reinforced IRTs correlated with differences in response rate, an outcome suggestive of the molecular control of response rate. This conclusion was complemented by the additional finding that the differences in molar reinforcement-feedback functions had little discernible impact on responding.


Spectroscopic (NMR, UV, FT-IR and FT-Raman) analysis and theoretical investigation of nicotinamide N-oxide with density functional theory.
The spectroscopic properties of the nicotinamide N-oxide (abbreviated as NANO, C(6)H(6)N(2)O(2)) were examined by FT-IR, FT-Raman, NMR and UV techniques. FT-IR and FT-Raman spectra in solid state were observed in the region 4000-400 cm(-1) and 3500-50 cm(-1), respectively. The (1)H and (13)C NMR spectra were recorded in DMSO. The UV absorption spectrum of the compound that dissolved in water was recorded in the range of 200-800 nm. The structural and spectroscopic data of the molecule in the ground state were calculated by using Density Functional Theory (DFT) employing B3LYP methods with the 6-311++G(d,p) basis set. The geometry of the molecule was fully optimized, vibrational spectra were calculated and fundamental vibrations were assigned on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method and PQS program. The optimized structure of compound was interpreted and compared with the reported experimental values. The observed vibrational wavenumbers, absorption wavelengths and chemical shifts were compared with calculated values. As a result, the optimized geometry and calculated spectroscopic data show a good agreement with the experimental results.


Knockdown of BTS may provide a new strategy to improve cadmium-phytoremediation efficiency by improving iron status in plants.
The identification of the key genes related to cadmium (Cd) tolerance and accumulation is a major element in genetically engineering improved plants for Cd phytoremediation. Owing to the similarity between the ionic hydrated radius of Cd2+ and Fe2+, this study investigated how the Cd tolerance and accumulation of Arabidopsis plants was affected by the knockdown of BTS, a gene that negatively regulates Fe nutrition. After exposure to 40 μM Cd, the BTS-knockdown mutant, bts-1, exhibited greater Fe nutrition and better growth than wild-type plants. In addition, the Cd concentration in both roots and shoots was approximately 50% higher in the bts-1 mutant than in wild-type plants. Consequently, the bts-1 mutant accumulated approximately 100% and 150% more Cd in the roots and shoots, respectively, than wild-type plants. Further study showed that Fe removal from the growth medium and inhibition of the Fe transporter gene, IRT1, removed the differences observed in the growth and Cd concentration of the bts-1 and wild-type plants, respectively. These results demonstrated that BTS knockdown improved Cd tolerance and accumulation in plants by improving Fe nutrition; thus, the knockdown of BTS via biotechnological pathways may represent a valuable strategy for the improvement in the efficiency of Cd phytoremediation.


Biomimetic method of emergency life channel urban planning in Wuhan using slime mold networks.
This study investigated a bio-inspired approach to planning optimal routes for urban hospital life channels to enable better responses to urban public security incidents. An experimental slime mold network and an origin-destination (OD) network model in which the nodes were tertiary hospitals in Wuhan were constructed. Correlation metrics of the two network models were used for network analysis and visualization. The experimental results showed that the slime mold network was better than the OD network in terms of global optimization. Furthermore, significant polarization of the influence value of urban hospital nodes resulted in a power-law distribution. This paper presents an urban planning method in which the biological mechanism of slime mold foraging is applied to construct shortest path networks in an emergency life channels. The results can be used to examine the relationship between urban roads and hospital nodes and the rational of global optimization distribution when planning the locations of new hospitals. A set of replicable and sustainable methods for conducting a biomimetic slime mold experiment to model real environments are presented. This approach provides a novel perspective for modeling emergency life channels.


Inhibition of lipid peroxidation in isolated rat liver mitochondria by the general anaesthetic propofol.
The effect of the general anaesthetic propofol (2,6-diisopropylphenol) on lipid peroxidation in rat liver mitochondria was assessed with the thiobarbituric acid (TBA) assay. Propofol was shown to inhibit the accumulation of TBA-reactive compounds after initiation of radical production by the addition of the ADP-Fe2+ complex. Analysis of kinetics showed that propofol caused a concentration-dependent delay as well as a decrease in the rate of the peroxidation process. 1H-NMR spectra of mitochondrial lipid extracts indicated that 95% of the added propofol remained intact after 30 min incubation under conditions of low oxidative stress. The ESR spectrum of propofol incubated in the presence of EDTA-Fe2+ and H2O2 as initiators of radical production showed a radical that was most likely a decomposition product of the primary phenoxy radical of propofol. It is concluded that (a) propofol acts as a chain reaction-breaking antioxidant by forming a stable radical and (b) propofol does not seem to be metabolized in mitochondria in vitro.


Correlation between chest x-ray and B-type natriuretic peptide in congestive heart failure.
B-Type natriuretic peptide (BNP) values greater than 400 pg/mL have high positive likelihood ratio (>10) for the diagnosis of clinical congestive heart failure (CHF). However, in patients with CHF, it is not known what correlation, if any, exists for the BNP levels above 400 pg/mL and the findings on the initial chest x-ray (CXR). Retrospective review of emergency department patients with CHF and initial BNP greater than 400 pg/mL. Descriptive statistics were analyzed and logistic regression was performed. Fifty-four patients mean age of 81.7 (SD, 8.2), 64.8% women. The mean BNP was 1493 pg/mL (SD, 1106). Only 68.5% had a finding of CHF on CXR. Logistic regression showed no correlation (Wald P = .568; R 2 = 0.8%). In patients with clinical CHF, there is no correlation between very high BNP levels (>400 pg/mL) and CXR readings. Clinicians should not be surprised to find patients with very high BNP levels but negative CXR.


Reduced mRNA and protein content of rho guanine nucleotide exchange factor (RhoGEF) in Bartter's and Gitelman's syndromes: relevance for the pathophysiology of hypertension.
Activation of RhoA/Rho kinase (ROK) pathway by angiotensin II (Ang II) is involved in the pathophysiology of hypertension and remodeling. In Bartter's and Gitelman's syndrome (BS/GS), the short-term and long-term signaling of Ang II are blunted. The BS/GS have also reduced expression and response on Ang II challenge of ROK, which indicate downregulation of RhoA/ROK pathway. As causes for RhoA/ROK downregulation in BS/GS, we hypothesized an alteration at the level of the upstream regulators of RhoA such as reduced expression of Rho guanine nucleotide exchange factor (RhoGEF), which links activation of G protein-coupled receptors to RhoA/ROK signaling or increased guanine nucleotide dissociation inhibitor (RhoGDI), which inhibits dissociation of GDP from GDI maintaining RhoA in an inactive state. In mononuclear cells of 9 BS/GS and 9 healthy controls (C), we looked at gene and protein expression (reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot) of RhoA, RhoGEF, and RhoGDI. In BS/GS RhoA gene and protein expression were not different from C. Also RhoGDI mRNA and protein levels were not different. On the contrary, p115RhoGEF mRNA and protein levels were reduced in BS/GS. Reduced p115RhoGEF may explain the downregulation of RhoA/ROK pathway in BS/GS. This is the first report of upstream regulators of RhoA level in BS/GS, a human clinical condition characterized by reduced vascular tone regulation. Because BS/GS represent the mirror image of derangements involved in hypertension, the reduced RhoGEF expression in BS/GS underlines a major impact of RhoA/ROK pathway on blood pressure regulation and confirms BS/GS as a good human model for exploring mechanisms involved in the pathophysiology of hypertension and remodeling.


[Correlation between the rate of protein and nucleic acid synthesis and the intensity of various glucose metabolic pathways in rat liver cells].
A sharp and strong suppression of protein synthesis by cycloheximide in liver cells of starving rats is paralleled with activation of RNA synthesis and glucose-6-phosphate dehydrogenase production. Subsequent reconstitution and stimulation of protein synthesis (6-12 hrs after cycloheximide injection) result in activation of hexokinase. Upon stimulation of DNA synthesis (48-60 hrs after cycloheximide injection) the activity of both enzymes is very low. Since glucose-6-phosphate dehydrogenase appears to be the limiting step of glucose decay via the pentose phosphate pathway, and hexokinase is the limiting step of glycolysis, it was assumed that RNA synthesis predominantly occurs via the pentose phosphate pathway, while that of proteins via glycolysis.


Gene expression analysis of Arc mRNA as a neuronal cell activity marker in the hippocampus and amygdala in two-way active avoidance test in rats.
Immediate early genes are widely used as neuronal cell activity markers in neuroscience. The present study investigated the relationship between their expression and abnormality in context fear conditioning. The learning test (two-way active avoidance test) was conducted in male rats administered with nonselective muscarinic antagonist scopolamine or selective dopamine D1-like receptor antagonist SCH 23390 at a dose level of 2.0 or 0.1mg/kg, respectively, for 4days. Expression levels of Arc and Fos mRNA in the hippocampus and amygdala were also evaluated on the second day of dosing by fluorescent in situ hybridization (FISH) and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Scopolamine had no effect on avoidance rate, but decreased freezing in the two-way active avoidance test. SCH 23390 decreased avoidance rate and increased freezing. In FISH and RT-qPCR assays, scopolamine decreased Arc mRNA in the hippocampus and amygdala, whereas SCH 23390 increased Arc mRNA in the hippocampus. By contrast, scopolamine and SCH 23390 did not change Fos mRNA expression compared to Arc mRNA expression. The results of the learning test indicated that scopolamine or SCH 23390 respectively inhibited fear or context conditioning in rats. Furthermore, alteration of the expression of Arc mRNA but not of Fos mRNA in the hippocampus and amygdala of the brain was suggested to be a sensitive neuronal cell activity marker to detect behavioral abnormality in the two-way active avoidance test.


Burn prevention mechanisms and outcomes: pitfalls, failures and successes.
Burns are responsible for significant mortality and morbidity worldwide and are among the most devastating of all injuries, with outcomes spanning the spectrum from physical impairments and disabilities to emotional and mental consequences. Management of burns and their sequelae even in well-equipped, modern burn units of advanced affluent societies remains demanding and extremely costly. Undoubtedly, in most low and middle income countries (LMICs) with limited resources and inaccessibility to sophisticated skills and technologies, the same standard of care is obviously not possible. Unfortunately, over 90% of fatal fire-related burns occur in developing or LMICs with South-East Asia alone accounting for over half of these fire-related deaths. If burn prevention is an essential part of any integrated burn management protocol anywhere, focusing on burn prevention in LMICs rather than treatment cannot be over-emphasized where it remains the major and probably the only available way of reducing the current state of morbidity and mortality. Like other injury mechanisms, the prevention of burns requires adequate knowledge of the epidemiological characteristics and associated risk factors, it is hence important to define clearly, the social, cultural and economic factors, which contribute to burn causation. While much has been accomplished in the areas of primary and secondary prevention of fires and burns in many developed or high-income countries (HICs) such as the United States due to sustained research on the epidemiology and risk factors, the same cannot be said for many LMICs. Many health authorities, agencies, corporations and even medical personnel in LMICs consider injury prevention to have a much lower priority than disease prevention for understandable reasons. Consequently, burns prevention programmes fail to receive the government funding that they deserve. Prevention programmes need to be executed with patience, persistence, and precision, targeting high-risk groups. Depending on the population of the country, burns prevention could be a national programme. This can ensure sufficient funds are available and lead to proper coordination of district, regional, and tertiary care centres. It could also provide for compulsory reporting of all burn admissions to a central registry, and these data could be used to evaluate strategies and prevention programmes that should be directed at behavioural and environmental changes which can be easily adopted into lifestyle. Particularly in LMICs, the emphasis in burn prevention should be by advocating change from harmful cultural practices. This needs to be done with care and sensitivity. The present review is a summary of what has already been accomplished in terms of burn prevention highlighting some of the successes but above all the numerous pitfalls and failures. Recognizing these failures is the first step towards development of more effective burn prevention strategies particularly in LMICs in which burn injury remains endemic and associated with a high mortality rate. Burn prevention is not easy, but easy or not, we have no options; burns must be prevented.


ChatGPT Is Equivalent to First-Year Plastic Surgery Residents: Evaluation of ChatGPT on the Plastic Surgery In-Service Examination.
ChatGPT is an artificial intelligence language model developed and released by OpenAI (San Francisco, CA) in late 2022. The aim of this study was to evaluate the performance of ChatGPT on the Plastic Surgery In-Service Examination and to compare it to residents' performance nationally. The Plastic Surgery In-Service Examinations from 2018 to 2022 were used as a question source. For each question, the stem and all multiple-choice options were imported into ChatGPT. The 2022 examination was used to compare the performance of ChatGPT to plastic surgery residents nationally. In total, 1129 questions were included in the final analysis and ChatGPT answered 630 (55.8%) of these correctly. ChatGPT scored the highest on the 2021 exam (60.1%) and on the comprehensive section (58.7%). There were no significant differences regarding questions answered correctly among exam years or among the different exam sections. ChatGPT answered 57% of questions correctly on the 2022 exam. When compared to the performance of plastic surgery residents in 2022, ChatGPT would rank in the 49th percentile for first-year integrated plastic surgery residents, 13th percentile for second-year residents, 5th percentile for third- and fourth-year residents, and 0th percentile for fifth- and sixth-year residents. ChatGPT performs at the level of a first-year resident on the Plastic Surgery In-Service Examination. However, it performed poorly when compared with residents in more advanced years of training. Although ChatGPT has many undeniable benefits and potential uses in the field of healthcare and medical education, it will require additional research to assess its efficacy.