Paenalcaligenes suwonensis sp. nov., isolated from spent mushroom compost.
A bacterial strain, ABC02-12(T), was isolated from spent mushroom compost, a waste product of button mushroom cultivation. Cells of the strain were Gram-stain-negative, catalase- and oxidase-positive, non-spore-forming, aerobic flagellated rods. Optimum growth occurred at 28 °C and pH 7.0. 16S rRNA gene sequence analysis showed that strain ABC02-12(T) shared the highest sequence similarities with Paenalcaligenes hominis CCUG 53761A(T) (96.0 %), Alcaligenes faecalis subsp. parafaecalis G(T) (95.7 %), Alcaligenes faecalis subsp. faecalis IAM 12369(T) (95.4 %) and Pusillimonas noertemannii BN9(T) (95.3 %). According to the phylogenetic tree, strain ABC02-12(T) formed a robust cluster with Paenalcaligenes hominis CCUG 53761A(T) and Paenalcaligenes hermetiae KBL009(T). The quinone system was ubiquinone Q-8 with minor amounts of Q-7. The major fatty acids (>5 % of total fatty acids) were C16 : 0, C16 : 1ω6c and/or C16 : 1ω7c (summed feature 3), C18 : 1ω7c and/or C18 : 1ω6c (summed feature 8), C17 : 0 cyclo, and iso-C16 : 1 I, C14 : 0 3-OH and/or an unknown fatty acid (summed feature 2). The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unknown aminolipid. Putrescine was the principal polyamine, with small amounts of 2-hydroxyputrescine and cadaverine. On the basis of the evidence presented in this study, strain ABC02-12(T) is a representative of a novel species within the genus Paenalcaligenes, for which the name Paenalcaligenes suwonensis sp. nov. is proposed. The type strain is ABC02-12(T) ( = KACC 16537(T) = NBRC 108927(T)).


Quantitative spatial evaluation of tumor-immune interactions in the immunotherapy setting of metastatic melanoma lymph nodes.
Immune cell infiltration into the tumor microenvironment is generally associated with favorable clinical outcomes in solid tumors. However, the dynamic interplay among distinct immune cell subsets within the tumor-immune microenvironment as it relates to clinical responses to immunotherapy remains unresolved. In this study, we applied multiplex immunofluorescence (MxIF) to spatially characterize tumor-immune interactions within the metastatic melanoma lymph node. Pretreatment, whole lymph node biopsies were evaluated from 25 patients with regionally metastatic melanoma who underwent subsequent anti-PD1 therapy. Cyclic MxIF was applied to quantitatively and spatially assess expression of 45 pathologist-validated antibodies on a single tissue section. Pixel-based single cell segmentation and a supervised classifier approach resolved 10 distinct tumor, stromal and immune cell phenotypes and functional expression of PD1. Single cell analysis across 416 pathologist-annotated tumor core regions of interest yielded 5.5 million cells for spatial evaluation. Cellular composition of tumor and immune cell subsets did not differ in the tumor core with regards to recurrence outcomes (p>0.05) however spatial patterns significantly differed in regional and paracrine neighborhood evaluations. Specifically, a regional community cluster comprised of primarily tumor and dendritic cells was enriched in patients that did not experience recurrence (p=0.009). By an independent spatial approach, cell-centric neighborhood analyses identified an enrichment for dendritic cells in cytotoxic T cell (CTL) and tumor cell-centric neighborhoods in the no recurrence patient response group (p<0.0001). Further evaluation of these neighborhoods identified an enrichment for CTL-dendritic cell interactions in patients that did not experience recurrence (p<0.0001) whereas CTL-macrophage interactions were more prevalent in CTL-centric neighborhoods of patients who experienced recurrence (p<0.0001). Overall, this study offers a more comprehensive evaluation of immune infiltrates and spatial-immune signatures in the metastatic tumor-immune microenvironment as it informs recurrence risk following immunotherapy.


G2 arrest in response to topoisomerase II inhibitors: the role of p53.
We have previously found that the overexpression of p53 causes G(2) arrest and represses the synthesis of cyclin-dependent kinase 1 and cyclin B1, two proteins required for cells to traverse from G(2) into M. G(2) arrest occurs in response to DNA damage caused by a variety of agents and treatments. Here, we investigate the role of p53 in the G(2) arrest that occurs in response to the topoisomerase inhibitors etoposide and merbarone. In HT1080 cells expressing a dominant-negative form of p53, treatment with etoposide still caused G(2) arrest, but the arrest could be overcome by additional treatment with caffeine, which inhibits the damage-responsive kinases ataxia telangiectasia mutated (ATM) and atm and rad3-related (ATR). However, caffeine could not overcome etoposide-induced G(2) arrest in HT1080 cells with functional p53. We conclude that etoposide activates two pathways, one of which depends on p53 and the other of which is sensitive to caffeine, and that either pathway is sufficient to activate G(2) arrest. Etoposide inhibits topoisomerase II by trapping the enzyme in a complex with cleaved DNA. Inhibition of topoisomerase II with merbarone, which does not stabilize a cleavage complex, causes G(2) arrest by a checkpoint that monitors the decatenation of chromatin. We find that caffeine can abrogate merbarone-induced G(2) arrest even in cells with functional p53, indicating that p53 does not contribute to the decatenation-sensitive response. Thus, p53 has a differential role in effecting G(2) arrest in response to topoisomerase II inhibitors, depending upon the mechanisms of action of the inhibitors tested.


Characterizing the Anticancer Treatment Trajectory and Pattern in Patients Receiving Chemotherapy for Cancer Using Harmonized Observational Databases: Retrospective Study.
Accurate and rapid clinical decisions based on real-world evidence are essential for patients with cancer. However, the complexity of chemotherapy regimens for cancer impedes retrospective research that uses observational health databases. The aim of this study is to compare the anticancer treatment trajectories and patterns of clinical events according to regimen type using the chemotherapy episodes determined by an algorithm. We developed an algorithm to extract the regimen-level abstracted chemotherapy episodes from medication records in a conventional Observational Medical Outcomes Partnership (OMOP) common data model (CDM) database. The algorithm was validated on the Ajou University School Of Medicine (AUSOM) database by manual review of clinical notes. Using the algorithm, we extracted episodes of chemotherapy from patients in the EHR database and the claims database. We also developed an application software for visualizing the chemotherapy treatment patterns based on the treatment episodes in the OMOP-CDM database. Using this software, we generated the trends in the types of regimen used in the institutions, the patterns of the iterative chemotherapy use, and the trajectories of cancer treatment in two EHR-based OMOP-CDM databases. As a pilot study, the time of onset of chemotherapy-induced neutropenia according to regimen was measured using the AUSOM database. The anticancer treatment trajectories for patients with COVID-19 were also visualized based on the nationwide claims database. We generated 178,360 treatment episodes for patients with colorectal, breast, and lung cancer for 85 different regimens. The algorithm precisely identified the type of chemotherapy regimen in 400 patients (average positive predictive value >98%). The trends in the use of routine clinical chemotherapy regimens from 2008-2018 were identified for 8236 patients. For a total of 12 regimens (those administered to the largest proportion of patients), the number of repeated treatments was concordant with the protocols for standard chemotherapy regimens for certain cases. In addition, the anticancer treatment trajectories for 8315 patients were shown, including 62 patients with COVID-19. A comparative analysis of neutropenia showed that its onset in colorectal cancer regimens tended to cluster between days 9-15, whereas it tended to cluster between days 2-8 for certain regimens for breast cancer or lung cancer. We propose a method for generating chemotherapy episodes for introduction into the oncology extension module of the OMOP-CDM databases. These proof-of-concept studies demonstrated the usability, scalability, and interoperability of the proposed framework through a distributed research network.


Statistical analysis of the individual variability of 1D protein profiles as a tool in ecology: an application to parasitoid venom.
Understanding the forces that shape eco-evolutionary patterns often requires linking phenotypes to genotypes, allowing characterization of these patterns at the molecular level. DNA-based markers are less informative in this aim compared to markers associated with gene expression and, more specifically, with protein quantities. The characterization of eco-evolutionary patterns also usually requires the analysis of large sample sizes to accurately estimate interindividual variability. However, the methods used to characterize and compare protein samples are generally expensive and time-consuming, which constrains the size of the produced data sets to few individuals. We present here a method that estimates the interindividual variability of protein quantities based on a global, semi-automatic analysis of 1D electrophoretic profiles, opening the way to rapid analysis and comparison of hundreds of individuals. The main original features of the method are the in silico normalization of sample protein quantities using pictures of electrophoresis gels at different staining levels, as well as a new method of analysis of electrophoretic profiles based on a median profile. We demonstrate that this method can accurately discriminate between species and between geographically distant or close populations, based on interindividual variation in venom protein profiles from three endoparasitoid wasps of two different genera (Psyttalia concolor, Psyttalia lounsburyi and Leptopilina boulardi). Finally, we discuss the experimental designs that would benefit from the use of this method.


Epidemiology of multiligament knee reconstruction.
The multiple-ligament-injured knee represents a special challenge, being an uncommon injury that is both severe and complicated to treat. Many studies have evaluated patients treated for this injury, but most are limited in their scope. The evaluation of this injury and its treatment using an administrative database might provide a different perspective. Using a large administrative database, we determined (1) the number of multiligament knee reconstructions in New York State, (2) the rate of 90-day hospital readmission, and (3) the frequency of subsequent knee surgery. We examined the rates of these outcomes as a function of diagnosis, admission type, discharge status, comorbidity burden, and patient demographic factors. We used the New York Department of Health Statewide Planning and Research Cooperative System (SPARCS), a database with information on patient characteristics, diagnoses, and treatments, to identify patients who underwent a multiligament procedure in a nonfederal facility from 1997 to 2005 using ICD-9-CM and Current Procedural Terminology codes. SPARCS collects data from all nonfederal acute care facilities, with an estimated reporting completeness of almost 99% for the years in this study. We evaluated data on patient age, sex, admission type, discharge status, and comorbidity burden (using Elixhauser comorbidities) and developed a multivariable logistic regression model to assess the influence of confounding variables. We identified 1032 patients in this database who underwent multiligament knee reconstruction in New York State from 1997 to 2005. The frequency of readmission within 90 days was 4.8% (n = 49). Readmission was more likely for patients who underwent inpatient multiligament reconstruction (odds ratio [OR] = 2.3; 95% CI: 1.2-4.4; p = 0.014), had a diagnosis of dislocation (OR = 2.2; 95% CI: 1.2-3.9; p = 0.011), or had various Elixhauser comorbidities, including chronic lung disease (OR = 6.4; 95% CI: 1.5-27.2; p = 0.013), fluid and electrolyte disorders (OR = 19.7; 95% CI: 2.5-155.7; p = 0.005), and anemia deficiency (OR = 5.6; 95% CI: 1.05-29.4; p = 0.044). Two hundred eighty-seven patients (28%) underwent subsequent knee surgery between their index procedure and 2006. Subsequent surgery was more likely for patients who underwent inpatient multiligament reconstruction (OR = 1.4; 95% CI: 1.1-1.9; p = 0.011) or were readmitted within 90 days of the index surgery (OR = 4.2; 95% CI: 2.3-7.6; p < 0.001). Our findings have the potential to aid clinicians in identifying their patients with multiligament reconstruction at highest risk for 90-day readmission and subsequent knee surgery. Future research, particularly large prospective studies evaluating surgical approaches and timing, will be critical in advancing the treatment of multiligament knee injuries. Level IV, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.


Effects of Fatigue and Postpartum Depression on Maternal Perceived Quality of Life (MAPP-QOL) in Early Postpartum Mothers.
This study was done to identify effects of fatigue and postpartum depression on quality of life in early postpartum mothers. The data were collected from 130 mothers at four general hospitals in J and M metropolitan cities. Instruments used to collect the data for the study were the Fatigue Scale developed by Pugh (1993); Postpartum Depression Scale developed by Cox, Holden & Sagovsky (1987), and the Quality of Life Scale developed by Hill, Aldag, Hekel, Riner, G., & Bloomfield (2006). Results showed that the mean for fatigue was 56.74, the mean for postpartum depression was 8.00+/-4.37 and mean for quality of life was 19.78. The quality of life variable showed statistically significant differences for the variable: age (F=3.20, p=.026). The relationship between fatigue and quality of life showed a significant negative correlation (r=-.44, p<.001). The relationship between postpartum depression and quality of life also showed a negative correlation (r=-.42, p<.001). The relationship between postpartum depression and fatigue showed a positive correlation (r=.59, p<.001). These factors explained 23% of the variance in quality of life. The results indicate that it is necessary to develop nursing intervention programs to improve quality of life in for early postpartum mothers.


Pentraxin 3 levels and correlation with disease severity in patients with acute rheumatic fever.
This study aims to investigate serum pentraxin 3 (PTX3) levels during acute episode of acute rheumatic fever (ARF) and their relationship with disease severity. The prospective study was conducted between January 2015 and December 2018 and included 52 ARF patients (22 girls, 30 boys, mean age 10.7±2.1 years; range, 5 to 16 years) experiencing an acute episode and 22 healthy children (13 girls, 9 boys, mean age 10.3±3.8 years; range, 5 to 16 years). ARF patients were classified into three groups based on the clinical course: isolated arthritis (n=17), mild carditis (n=19), and moderate/severe carditis (n=16). Blood samples were collected from all patients before treatment and from the healthy children in the control group to measure PTX3 levels. PTX3 was measured using sandwich enzyme-linked immunosorbent assay method. Plasma PTX3 levels were significantly higher in ARF group compared to the control group (4.7±5.2 and 1.2±1.7 ng/mL, p<0.001). Subgroup analysis of serum PTX3 levels in ARF patients with isolated arthritis, mild carditis, and moderate/severe carditis (3.2±3.1 ng/mL, 4.3±5 ng/mL, and 6.7±6.6 ng/mL, respectively) showed that serum PTX3 was significantly higher in the moderate/severe carditis group compared to the other groups (p<0.05). Analysis of echocardiographic data showed that serum PTX3 was positively correlated with left ventricular end-diastolic diameter, left atrial diameters, and mitral A velocity and negatively correlated with E/A ratio (p<0.05; r=0.231, 0.402, 0.562, -0.586, respectively). High PTX3 level during an acute episode of ARF may help predict the clinical course and the severity of accompanying carditis. However, prospective studies with larger sample sizes are needed.


Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: exploratory analysis of a randomized trial.
Randomized data on statins for primary prevention in older persons are limited, and the relative hazard of cardiovascular disease associated with an elevated cholesterol level weakens with advancing age. To assess the efficacy and safety of rosuvastatin in persons 70 years or older. Secondary analysis of JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin), a randomized, double-blind, placebo-controlled trial. 1315 sites in 26 countries randomly assigned participants in JUPITER. Among the 17 802 participants randomly assigned with low-density lipoprotein (LDL) cholesterol levels less than 3.37 mmol/L (<130 mg/dL) and high-sensitivity C-reactive protein levels of 2.0 mg/L or more without cardiovascular disease, 5695 were 70 years or older. Participants were randomly assigned in a 1:1 ratio to receive 20 mg of rosuvastatin daily or placebo. The primary end point was the occurrence of a first cardiovascular event (myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes). The 32% of trial participants 70 years or older accrued 49% (n = 194) of the 393 confirmed primary end points. The rates of the primary end point in this age group were 1.22 and 1.99 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio, 0.61 [95% CI, 0.46 to 0.82]; P < 0.001). Corresponding rates of all-cause mortality in this age group were 1.63 and 2.04 (hazard ratio, 0.80 [CI, 0.62 to 1.04]; P = 0.090). Although no significant heterogeneity was found in treatment effects by age, absolute reductions in event rates associated with rosuvastatin were greater in older persons. The relative rate of any serious adverse event among older persons in the rosuvastatin versus placebo group was 1.05 (CI, 0.93 to 1.17). Effect estimates from this exploratory analysis with age cut-point chosen after trial completion should be viewed in the context of the overall trial results. In apparently healthy older persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin reduces the incidence of major cardiovascular events. AstraZeneca.


Characterization of cellulolytic bacterial cultures grown in different substrates.
Nine aerobic cellulolytic bacterial cultures were obtained from the Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Culture (DSMZ) and the American Type Culture Collection (ATCC). The objectives of this study were to characterize the cellulolytic bacteria and to determine the optimum moisture ratio required for solid state fermentation (SSF) of palm kernel cake (PKC). The bacteria cultures were grown on reconstituted nutrient broth, incubated at 30°C and agitated at 200 rpm. Carboxymethyl cellulase, xylanase, and mannanase activities were determined using different substrates and after SSF of PKC. The SSF was conducted for 4 and 7 days with inoculum size of 10% (v/w) on different PKC concentration-to-moisture ratios: 1 : 0.2, 1 : 0.3, 1 : 0.4, and 1 : 0.5. Results showed that Bacillus amyloliquefaciens 1067 DSMZ, Bacillus megaterium 9885 ATCC, Paenibacillus curdlanolyticus 10248 DSMZ, and Paenibacillus polymyxa 842 ATCC produced higher enzyme activities as compared to other bacterial cultures grown on different substrates. The cultures mentioned above also produced higher enzyme activities when they were incubated under SSF using PKC as a substrate in different PKC-to-moisture ratios after 4 days of incubation, indicating that these cellulolytic bacteria can be used to degrade and improve the nutrient quality of PKC.


Molecular basis of pollen-related food allergy: identification of a second cross-reactive IgE epitope on Pru av 1, the major cherry (Prunus avium) allergen.
Birch (Betula verrucosa) pollen-associated food allergy is a well-characterized syndrome, which is due to the cross-reactivity of IgE antibodies to homologous allergens in various foods. One crossreacting area on the major birch pollen allergen Bet v 1 and its homologue in cherry (Prunus avium) Pru av 1 has already been identified. This is the so-called 'P-loop' region, which encompasses amino acid residues around position 45 and is found on the two virtually identical tertiary protein structures. We tried to determine an additional IgE cross-reacting patch on Pru av 1 and Bet v 1. The putative IgE-binding region on Pru av 1 was localized with a mAb (monoclonal antibody) that was generated against Bet v 1, and cross-reacts with several Bet v 1 homologues in food and inhibits the binding of patients' IgE to Pru av 1. mAb reactivity pattern was analysed and amino acid positions 28 and 108 of Pru av 1 were selected and mutated by site-directed mutagenesis. The Pru av 1 mutants were produced as recombinant proteins and characterized for their folding, mAb- and IgE-binding capacity and allergenic potency with a cellular assay using the humanized rat basophilic leukaemia cell line RBL-25/30. Amino acid position 28 is involved in a second major IgE-binding region on Pru av 1 and probably on Bet v 1. The identification of this second major IgE-binding region is an essential prerequisite to understand the phenomenon of cross-reactivity and its clinical consequences, and to produce hypoallergenic proteins for an improved immunotherapy of type I allergy.


Effective policies to promote sugar reduction in soft drinks: lessons from a comparison of six European countries.
Many countries have sought to incentivise soft drinks manufacturers to reduce sugar in their products as part of efforts to address a growing prevalence of obesity. Are their policies effective? Using a difference-in-differences design, we compared trends in the sugar content of 10 695 new sugar-sweetened beverages (SSB) launched between 2010 and 2019 in six European markets, including the UK and France (taxes designed to incentivise reformulation), the Netherlands (policy based on voluntary agreements to reduce sugar), Germany, Italy and Spain (no national policies). The announcement in 2016 and adoption in 2018 of the UK tax led to yearly reductions in average sugar content of 17% (95% CI: 15-19%) to 31% (13-48%) between 2016 and 2019, compared to 2015, while the 2018 French tax produced a 6% (95% CI: 5-7%) sugar reduction only in 2018, compared to 2017, shortly after it was redesigned to provide a stronger incentive for reformulation. Voluntary agreements implemented in the Netherlands in 2014 led to an 8% (95% CI: 4-13%) sugar reduction only in 2015, compared to 2013. The analysis supports the conclusions that sugar reductions in new SSBs have been greater in countries that have adopted specific policies to encourage them; a sugar-based tax design encourages more sugar reductions than a volume-based tax design; the tax rate and the amount of the tax reduction from switching to the next lower tier in a sugar-based tax design may be critical to incentivize reformulation.


Effects of including soy protein in a blood cholesterol-lowering diet on markers of cardiac risk in men and in postmenopausal women with and without hormone replacement therapy.
Increased consumption of soy foods has been associated with reduction in low density lipoprotein cholesterol (LDL-C) in both clinical and observational studies. However, it is not clear whether adding soy to a low-fat diet has additional lipid-lowering benefits, and few previous studies have examined these effects in women using hormone replacement therapy (HRT+). We tested whether adding soy protein to a low-fat, high-fiber, Step I diet improved cardiac risk markers in 18 postmenopausal women and 14 men with hypercholesterolemia and examined whether concurrent use of HRT altered diet responsiveness. Diets were matched for macronutrient content, and all food was provided. After 3 weeks on the Step I diet, subjects were randomized to diets (6 weeks) containing 25 g/day protein isolate from soy or cow's milk, with crossover. The soy treatment contained 90 mg/day isoflavones. Lipids, vascular cell adhesion molecule-1 (VCAM-1), p-selectin, and urinary isoflavonoids were measured at the end of each diet. In men and HRT- women only, there were significant reductions in LDL-C (-17.3%), high-density lipoprotein cholesterol (HDL-C) (-15.3%), and triglycerides (-11.5%) during the Step I diet, and soy had no additional effects. At study entry, HRT+ women had lower LDL-C and higher triglycerides than men. Their LDL-C was unchanged, and triglycerides were significantly reduced (-15.1%) by the Step I diets. Isoflavonoid excretion was unrelated to diet response or HRT status. In men and HRT- women, the diets significantly lowered LDL-C, independent of soy intake. In HRT+ women, the diets improved triglycerides without lowering HDL-C.


Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated cell response to Listeria infection.
Cell autonomous responses to intracellular bacteria largely depend on reorganization of gene expression. To gain isoform-level resolution of these modes of regulation, we combined long- and short-read transcriptomic analyses of the response of intestinal epithelial cells to infection by the foodborne pathogen Listeria monocytogenes. Among the most striking isoform-based types of regulation, expression of the cellular stress response regulator CIRBP (cold-inducible RNA-binding protein) and of several SRSFs (serine/arginine-rich splicing factors) switched from canonical transcripts to nonsense-mediated decay-sensitive isoforms by inclusion of 'poison exons'. We showed that damage to host cell membranes caused by bacterial pore-forming toxins (listeriolysin O, perfringolysin, streptolysin or aerolysin) led to the dephosphorylation of SRSFs via the inhibition of the kinase activity of CLK1, thereby driving CIRBP alternative splicing. CIRBP isoform usage was found to have consequences on infection, since selective repression of canonical CIRBP reduced intracellular bacterial load while that of the poison exon-containing isoform exacerbated it. Consistently, CIRBP-bound mRNAs were shifted towards stress-relevant transcripts in infected cells, with increased mRNA levels or reduced translation efficiency for some targets. Our results thus generalize the alternative splicing of CIRBP and SRSFs as a common response to biotic or abiotic stresses by extending its relevance to the context of bacterial infection.


Effectiveness of community health worker training programmes for cardiovascular disease management in low-income and middle-income countries: a systematic review.
Community health workers (CHWs) are increasingly being tasked to prevent and manage cardiovascular disease (CVD) and its risk factors in underserved populations in low-income and middle-income countries (LMICs); however, little is known about the required training necessary for them to accomplish their role. This review aimed to evaluate the training of CHWs for the prevention and management of CVD and its risk factors in LMICs. A search strategy was developed in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and five electronic databases (Medline, Global Health, ERIC, EMBASE and CINAHL) were searched to identify peer-reviewed studies published until December 2016 on the training of CHWs for prevention or control of CVD and its risk factors in LMICs. Study characteristics were extracted using a Microsoft Excel spreadsheet and quality assessed using Effective Public Health Practice Project's Quality Assessment Tool. The search, data extraction and quality assessment were performed independently by two researchers. The search generated 928 articles of which 8 were included in the review. One study was a randomised controlled trial, while the remaining were before-after intervention studies. The training methods included classroom lectures, interactive lessons, e-learning and online support and group discussions or a mix of two or more. All the studies showed improved knowledge level post-training, and two studies demonstrated knowledge retention 6 months after the intervention. The results of the eight included studies suggest that CHWs can be trained effectively for CVD prevention and management. However, the effectiveness of CHW trainings would likely vary depending on context given the differences between studies (eg, CHW demographics, settings and training programmes) and the weak quality of six of the eight studies. Well-conducted mixed-methods studies are needed to provide reliable evidence about the effectiveness and cost-effectiveness of training programmes for CHWs.


10.7 Gb/s reflective electroabsorption modulator monolithically integrated with semiconductor optical amplifier for colorless WDM-PON.
We demonstrated 10.7 Gb/s reflective electroabsorption modulator monolithically integrated with semiconductor optical amplifier (REAM-SOA) using simplified fabrication process. Good performance at 10.7 Gb/s was obtained with an extinction ratio of > 10 dB and a power penalty of < 1 dB at a 10(-9) bit error rate (BER) up to 20 km transmission. The device operated over a 50 nm spectral range within 1 dB received power variation at a 10(-9) BER.


Hemispheric language dominance in children demonstrated by functional magnetic resonance imaging.
The objective of this study was to demonstrate hemispheric language dominance in normal children. Fifteen normal children were evaluated with functional magnetic resonance imaging (MRI) using an age-related silent word spelling paradigm. The data were analyzed with the cross-correlation method, and lateralization indices were calculated in language regions as determined by Talairach coordinates. Activation foci were detected in the left inferior frontal area and were strongly lateralized, with language lateralization indices of 0.74 +/- 0.21 (age 7-12 years, nine subjects), and 0.79 +/- 0.18 (13-18 years, six subjects). The indices were similar to those for adults (0.83 +/- 0.21, four subjects). Our study established that language is strongly lateralized to the left hemisphere in children as young as 7 years of age.


An objective and standardized test of foot function: normative values and validation in patients with reflex sympathetic dystrophy.
To describe and obtain normative values for an objective and standardized test of foot function, and to validate the test in patients with impaired function of 1 leg. A series of 4 standardized and objectively measured subtests, representing common foot activities in daily living, was devised. University hospital. Normative values were obtained for 100 healthy patients between 20 and 70 years of age. For validation purposes, the test was also performed by 20 patients diagnosed with reflex sympathetic dystrophy of 1 foot. Several basic aspects of individual foot function were evaluated: (1) forward and backward shifting (FBS) of a foot panel; (2) lateral shifting (LS) of a foot panel; (3) alternately touching 2 bells (TB); and (4) depressing a pedal (DP). (The tests were performed while seated; hence, they are applicable to patients unable to walk.) Comparison with results on a battery of other clinical function tests was assessed. The intrarater and interrater reliabilities of the test were high (eg, intrarater correlation coefficients ranged from .74 to .93; interrater from .85 to .99). Results were influenced by sex and dominance, but were not influenced by height, weight, or shoe size. Age and leisure activities involving foot function influenced 1 subtest only (depressing a pedal). Results of the affected side in patients were higher than normative values although, to a lesser extent, the same was true for the unaffected side. Footboard results did not correlate with results of other function tests, except myometry, suggesting that it provides additional information. In contrast to the other tests, and like myometry, the footboard distinguished patients who were crutch dependent from those who were not. The footboard is a valuable addition to current tests for assessing foot function.


Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns.
Upon delivery, the neonate is exposed for the first time to a wide array of microbes from a variety of sources, including maternal bacteria. Although prior studies have suggested that delivery mode shapes the microbiota's establishment and, subsequently, its role in child health, most researchers have focused on specific bacterial taxa or on a single body habitat, the gut. Thus, the initiation stage of human microbiome development remains obscure. The goal of the present study was to obtain a community-wide perspective on the influence of delivery mode and body habitat on the neonate's first microbiota. We used multiplexed 16S rRNA gene pyrosequencing to characterize bacterial communities from mothers and their newborn babies, four born vaginally and six born via Cesarean section. Mothers' skin, oral mucosa, and vagina were sampled 1 h before delivery, and neonates' skin, oral mucosa, and nasopharyngeal aspirate were sampled <5 min, and meconium <24 h, after delivery. We found that in direct contrast to the highly differentiated communities of their mothers, neonates harbored bacterial communities that were undifferentiated across multiple body habitats, regardless of delivery mode. Our results also show that vaginally delivered infants acquired bacterial communities resembling their own mother's vaginal microbiota, dominated by Lactobacillus, Prevotella, or Sneathia spp., and C-section infants harbored bacterial communities similar to those found on the skin surface, dominated by Staphylococcus, Corynebacterium, and Propionibacterium spp. These findings establish an important baseline for studies tracking the human microbiome's successional development in different body habitats following different delivery modes, and their associated effects on infant health.


Rehabilitation of hand burn injuries: current updates.
The improved short and long term survival rate of individuals with large burn injuries has made rehabilitation for optimal recovery of the patient increasingly important. Burn injury to the hands worsens the prospect of functional recovery and good quality of life in single events, especially when included in larger burns. The purpose of this paper is to present a narrative review of examination strategies used for children with burn injuries to the hands in the acute, intermediate and long term stages of rehabilitation, and apply these concepts to selected treatments, using a case that is representative of this complex patient population. The model of health described by the World Health Organisation provided the framework for the review, to structure the review in the domains of body structures and body functions, functional activities and participation in life roles. The lack of consensus in the burn literature regarding the most appropriate outcome measures and interventions necessitates futures research and long term outcome studies to identify, predict and prevent the difficulties patients may face over their lifespan.


Comparative Osteogenesis of Three Clinical Bone Graft Materials: An In Vivo Study.
To investigate bone regeneration among three different bone graft materials in a rat calvarum model. A total of 24 rats had two 5-mm defects placed per calvarial. Rats were divided into four groups: bovine xenograft (XG), demineralized bone matrix (DBM), mineralized bone graft (MBG), and collagen membrane control (CC). Within each group, samples were collected at two time points: 4 weeks (T4) and 8 weeks (T8). Bone regeneration was assessed by microcomputed tomography (micro-CT) imaging and was analyzed using MATLAB software. Additionally, the fixed samples were subsequently demineralized for immunohistochemistry and histomorphometry. Slides were mounted and stained with hematoxylin and eosin (H&E) stain as well as bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (RUNX2) markers. The numbers of positive cells/area were calculated for each group and analyzed. At 4 weeks, DBM showed low mineral density (7.7%) compared to the control (25.2%), but increased dramatically at 8 weeks (DBM, T8 = 27.6%; CC, T8 = 27.2%). Xenograft material showed an increase in mineral desnity between T4 and T8 (XG, T4 = 25.0%; XG, T8 = 32.3%). MBG remained consistent over the 8-week trial period (MBG, T4 = 30.4%; MBG, T8 = 30.4%). BMP-2 expression was present in cells adherent to all graft materials. RUNX2 expression was also observed in cells adherent to all graft materials, indicating that during the 4- to 8-week healing period, all materials supported osteogenesis. Compared to other materials, the DBM had high osteoinductive properties during the 4- to 8-week time period based on increased mineral content. All materials were associated with immunohistologic evidence of osteogenesis in the rat calvarial defect model.


Risk factors for wound complications after surgery for gynecologic malignancies.
Factors in wound complications such as surgical duration and suture methods are surgeon-side problems. The purpose of the present study was to retrospectively evaluate the incidence of wound complications in patients who underwent wound closure with stainless steel staples or subcuticular sutures in surgery for gynecologic malignancies and to retrospectively determine the risk factors for wound complications. From April 2007 through March 2012, a cohort of 317 consecutive patients undergoing surgery for gynecologic malignancies was evaluated in the retrospective study. The skin was closed with stainless steel staples before March 2010 (staples group). From April 2010, the skin was closed by subcuticular suturing (subcuticular group). We compared the incidence of wound complications between 2 groups and evaluated independent multivariate associations with the effect of clinical parameters on occurrence of wound complications. The incidence of wound disruption was 7.3% (23/317): 12.1% (17/140) in the staples group and 3.4% (6/177) in the subcuticular group (P = 0.0029). The incidence of wound infection was 2.5% (8/317): 5.0% (7/140) in the staples group and 0.6% (1/177) in the subcuticular group (P = 0.0124). Multivariate analyses performed with wound disruption as the end point revealed long-term steroid treatment, subcutaneous thickness, and skin staples as independent predictors. Subcutaneous thickness and skin staples were independent factors significantly associated with the possibility of wound infection. The findings of the present study indicated that risk factors for wound complications after surgeries for gynecologic malignancies include, as a surgeon-side problem, the use of staples for skin closure, and as a patient-side problem, a subcutaneous thickness of more than 30 mm.


Pentavalent antimonial inhibition of the osmotic effect of oxytocin on the isolated toad bladder.
The inhibition of osmotic stimulated water flow in the isolated toad bladder by 0.1 mM sodium stibogluconate (pentavalent antimony) is described. Pentavalent antimony on the serosal surface significantly inhibited oxytocin-induced water flow but when the drug was added to the mucosal surface only the effect of low oxytocin concentrations was reduced. The phosphodiesterase inhibitor pentoxifylline, when present on the serosal side, blocks the effect of pentavalent antimony on stimulated water flow. No effect was detected when indomethacin was present on the serosal side. It is suggested that phosphodiesterase activation might play a role in the mechanism of pentavalent antimonial inhibition of oxytocin-induced water flow in the isolated toad bladder. The effect obtained when sodium stibogluconate on the serosal side was replaced with antimony pentachloride (SbCl5) supports the view that the metal in the molecule is responsible for the inhibition of the effect of oxytocin.


Meta-analysis: griseofulvin efficacy in the treatment of tinea capitis.
Despite its long history in clinical use, reported efficacy rates of griseofulvin remain highly variable. A meta-analysis of clinical trials of griseofulvin use in tinea capitis was performed to determine mean griseofulvin efficacy. A review of the literature identified 7 studies. When all 7 studies were pooled, the overall mean effective cure (negative KOH and culture) of griseofulvin at 4 to 6 weeks posttreatment was 73.4% +/- 7% (7 studies, n = 438 patients). Higher efficacy rates appeared to be reported with the use of higher dosages of griseofulvin (> 18 mg/kg/d). When broken down by species, the mean efficacy for Trichophyton and Microsporum were 67.6% +/- 9% (5 studies, n = 396) and 88.1% +/- 5% (2 studies, n = 42 patients), respectively. Based on these studies, griseofulvin efficacy has remained consistently high over the past decade. Both genera showed good efficacy with griseofulvin therapy given from 6 to 8 weeks. Griseofulvin remains an effective therapy for tinea capitis.


Electrodialytic per- and polyfluoroalkyl substances (PFASs) removal mechanism for contaminated soil.
Contamination of soils with per- and polyfluoroalkyl substances (PFASs) is a global problem, in particular at fire-fighter training sites due to the usage of PFAS-containing aqueous fire-fighting foams (AFFFs). In this study, an electrodialytic remediation method was applied for the first time to remove PFASs from contaminated soil. The electrodialytic remediation system was evaluated in a laboratory-scale experiment with current densities of 0.19 mA cm-2 and 0.38 mA cm-2 over 21 days, using PFAS-contaminated soil from a fire-fighter training site at Stockholm Arlanda Airport, Sweden. Of the 23 PFASs targeted, significant (p < 0.05) PFAS electromigration towards the anode was observed for C3-C7 perfluoroalkyl carboxylates (PFCAs) (PFBA, PFPeA, PFHxA, PFOA) and C4, C6, and C8 perfluoroalkane sulfonates (PFSAs) (PFBS, PFHxS, PFOS) since these PFASs were predominantly negatively charged. In contrast to the electromigration of the charged PFASs, N-methyl perfluorooctane sulfonamide (MeFOSA), perfluorooctane sulfonamidoacetic acid (FOSAA) and ethyl FOSAA (EtFOSAA) showed significant (p < 0.05) transport towards the cathode, which is probably attributed to electro-osmotic flow of these predominantly neutral PFASs. Mass balance calculations showed that for the shortest-chained PFASs (i.e., PFBA, PFPeA, PFHxA, PFBS, and PFHxS), up to 20% was extracted from the soil to the anolyte, which showed that electrodialysis is a possible in-situ remediation technique for PFAS-contaminated soil.


Vanadyl sulfate protects against streptozotocin-induced morphological and biochemical changes in rat aorta.
The aim of this study was to investigate the protective effects of vanadyl sulfate on aorta tissue of normal and streptozotocin (STZ)-induced diabetic rats, morphologically and biochemically. The animals were made diabetic by an intraperitoneal injection of streptozotocin (65 mg/kg) and vanadyl sulfate (100 mg/kg) that was given every day for 60 days by gavage technique to rats. Under the light and transmission electron microscopes, hypertrophy of the vessel wall, focal disruption in the elastic lamellae, an increase in thickness of total aortic wall, tunica intima, subendothelial space and adventitial layer, and a disorganization in smooth muscular cells of the tunica media were observed in diabetic animals. The aorta lipid peroxidation (LPO) levels were significantly increased and the aorta glutathione (GSH) levels were significantly reduced in STZ diabetic rats. In diabetic rats administered vanadyl sulfate for 60 days, aorta LPO levels significantly decreased and the aorta GSH level significantly increased. In conclusion, in vivo treatment with vanadyl sulfate of diabetic rats prevented the morphological and biochemical changes observed in thoracic aorta of diabetic animals.


TACTICS VR Stroke Telehealth Virtual Reality Training for Health Care Professionals Involved in Stroke Management at Telestroke Spoke Hospitals: Module Design and Implementation Study.
Stroke management in rural areas is more variable and there is less access to reperfusion therapies, when compared with metropolitan areas. Delays in treatment contribute to worse patient outcomes. To improve stroke management in rural areas, health districts are implementing telestroke networks. The New South Wales Telestroke Service provides neurologist-led telehealth to 23 rural spoke hospitals aiming to improve treatment delivery and patient outcomes. The training of clinical staff was identified as a critical aspect for the successful implementation of this service. Virtual reality (VR) training has not previously been used in this context. We sought to develop an evidence-based VR training module specifically tailored for stroke telehealth. During implementation, we aimed to assess the feasibility of workplace deployment and collected feedback from spoke hospital staff involved in stroke management on training acceptability and usability as well as perceived training impact. The TACTICS VR Stroke Telehealth application was developed with subject matter experts. During implementation, both quantitative and qualitative data were documented, including VR use and survey feedback. VR hardware was deployed to 23 rural hospitals, and use data were captured via automated Wi-Fi transfer. At 7 hospitals in a single local health district, staff using TACTICS VR were invited to complete surveys before and after training. TACTICS VR Stroke Telehealth was deployed to rural New South Wales hospitals starting on April 14, 2021. Through August 20, 2023, a total of 177 VR sessions were completed. Survey respondents (n=20) indicated a high level of acceptability, usability, and perceived training impact (eg, accuracy and knowledge transfer; mean scores 3.8-4.4; 5=strongly agree). Furthermore, respondents agreed that TACTICS VR increased confidence (13/18, 72%), improved understanding (16/18, 89%), and improved awareness (17/18, 94%) regarding stroke telehealth. A comparison of matched pre- and posttraining responses revealed that training improved the understanding of telehealth workflow practices (after training: mean 4.2, SD 0.6; before training: mean 3.2, SD 0.9; P<.001), knowledge on accessing stroke telehealth (mean 4.1, SD 0.6 vs mean 3.1, SD 1.0; P=.001), the awareness of stroke telehealth (mean 4.1, SD 0.6 vs mean 3.4, SD 0.9; P=.03), ability to optimally communicate with colleagues (mean 4.2, SD 0.6 vs mean 3.7, SD 0.9; P=.02), and ability to make improvements (mean 4.0, SD 0.6 vs mean 3.5, SD 0.9; P=.03). Remote training and deployment were feasible, and limited issues were identified, although uptake varied widely (0-66 sessions/site). TACTICS VR Stroke Telehealth is a new VR application specifically tailored for stroke telehealth workflow training at spoke hospitals. Training was considered acceptable, usable, and useful and had positive perceived training impacts in a real-world clinical implementation context. Additional work is required to optimize training uptake and integrate training into existing education pathways.


Prevalence and disposition of drugs of abuse and opioid treatment drugs in oral fluid.
Testing oral fluid for drugs of abuse has been studied under many conditions but rarely has been evaluated in large population databases. We evaluated oral fluid tests in a database from a commercial laboratory in the United Kingdom composed of 8679 confirmed positive results. The results originated from 635,000 specimens collected over the period of May 2004 through September 2006. Oral fluid specimens were collected with the Intercept oral fluid collection device, screened by enzyme immunoassay, and confirmed by GC-MS or GC-MS-MS. The database was organized by collection settings (legal/treatment, N = 8198 specimens; and workplace, N = 481 specimens) and by drug groups (without consideration of collection setting). The drug groups were as follows (number of confirmed positives): amphetamines (468); benzodiazepines (892); buprenorphine (276); cannabinoids (725); cocaine (1443); methadone (998); and opiates (5739). The goal of the study was to provide drug/metabolite prevalence data, concentrations, and drugs/metabolite patterns encountered in oral fluid. Comparison of results by collection setting indicated differences in relative frequency, primarily for opiates and cannabinoids. Opiate positives were most frequently observed for specimens collected in legal/treatment settings, whereas cannabinoids were most frequently reported in the workplace. An array of information on drug and metabolite occurrences and concentration arose from evaluation of the data by drug groups. Amphetamine was the predominant drug reported for the Amphetamines Group; approximately 10% were also positive for MDA and/or MDMA; and methamphetamine was rarely reported. Multiple combinations of diazepam, nordiazepam, oxazepam, temazepam, chlordiazepoxide, and lorazepam were reported for the Benzodiazepine Group. Buprenorphine, an opioid treatment drug, was the predominant analyte reported, but low concentrations of norbuprenorphine were frequently reported. THC was the predominant analyte reported in the Cannabinoids Group and was frequently reported in combination with cannabidiol and cannabinol. THCCOOH was reported in only 10.8% of these specimens and was never reported in the absence of THC. HO-THC was reported in 5.7% of the specimens. In the Cocaine Group, cocaine was present, often in combination with BZE, but also as the sole analyte in 17.3% of the specimens. AEME and cocaethylene were reported in 10.4% and 5.5% of the specimens. Methadone, another opioid treatment drug, was reported in all specimens for the Methadone Group; EDDP was reported in 30.1% of the specimens. In the Opiates Group, morphine, codeine and 6-acetylmorhine were most frequently reported, often in combination. The frequency of detection of 6-acetylmorphine when morphine was present (N = 4575 specimens) was 77.5%. Surprisingly, heroin (19.0%; N = 1091 specimens) and 6-acetylcodeine (24.9%; N = 1431 specimens) were frequently reported. The results from analysis of this large oral fluid database offer a rich mixture of new information on detection frequency, drug and metabolite patterns, and concentration data on drugs of abuse.


Necrotizing pneumonia and septic shock: suspecting CA-MRSA in patients presenting to Canadian emergency departments.
We report a case of fatal necrotizing pneumonia and sepsis caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in an otherwise well, 48-year-old Canadian man with type 2 diabetes mellitus who had travelled to Texas. Despite therapy that included intravenous antibiotics, intravenous immune globulin and other supportive measures, the patient succumbed to his illness. Recently, CA-MRSA pneumonia has been reported in several countries. The virulence of this organism may in part be related to its ability to produce toxins, such as Panton-Valentine leukocidin. As rates of CA-MRSA increase worldwide, physicians should be aware of the potential for MRSA to cause life-threatening infections in patients presenting to Canadian emergency departments (EDs). Necrotizing pneumonia caused by MRSA must be considered in the differential diagnosis of acute, severe respiratory illness. Early recognition of this syndrome in the ED may help physicians initiate appropriate antibiotic therapy in a timely manner.


Congenital lobar emphysema: is surgery routinely necessary?
Congenital lobar emphysema (CLE) is a rare congenital abnormality characterised by overinflation of a pulmonary lobe. Its aetiology is unknown. The management of CLE has traditionally been surgical. A newborn boy with a birthweight of 2.5 kg was delivered at full-term by caesarian section due to food delivery. There was no marked respiratory distress at birth, and little meconium stained liquor was seen on the skin. The initial diagnosis was meconium aspiration syndrome. After computed tomography of the thorax, CLE was diagnosed. The patient was observed throughout for a week and the CT of the thorax was repeated, which revealed that the emphysema had resolved. The nonoperative approach should be considered in asymptomatic patients with CLE.


Roland-Morris Disability Questionnaire and Oswestry Disability Index: Which Has Better Measurement Properties for Measuring Physical Functioning in Nonspecific Low Back Pain? Systematic Review and Meta-Analysis.
Physical functioning is a core outcome domain to be measured in nonspecific low back pain (NSLBP). A panel of experts recommended the Roland-Morris Disability Questionnaire (RMDQ) and Oswestry Disability Index (ODI) to measure this domain. The original 24-item RMDQ and ODI 2.1a are recommended by their developers. The purpose of this study was to evaluate whether the 24-item RMDQ or the ODI 2.1a has better measurement properties than the other to measure physical functioning in adult patients with NSLBP. Bibliographic databases (MEDLINE, Embase, CINAHL, SportDiscus, PsycINFO, and Google Scholar), references of existing reviews, and citation tracking were the data sources. Two reviewers selected studies performing a head-to-head comparison of measurement properties (reliability, validity, and responsiveness) of the 2 questionnaires. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the methodological quality of these studies. The studies' characteristics and results were extracted by 2 reviewers. A meta-analysis was conducted when there was sufficient clinical and methodological homogeneity among studies. Nine articles were included, for a total of 11 studies assessing 5 measurement properties. All studies were classified as having poor or fair methodological quality. The ODI displayed better test-retest reliability and smaller measurement error, whereas the RMDQ presented better construct validity as a measure of physical functioning. There was conflicting evidence for both instruments regarding responsiveness and inconclusive evidence for internal consistency. The results of this review are not generalizable to all available versions of these questionnaires or to patients with specific causes for their LBP. Based on existing head-to-head comparison studies, there are no strong reasons to prefer 1 of these 2 instruments to measure physical functioning in patients with NSLBP, but studies of higher quality are needed to confirm this conclusion. Foremost, content, structural, and cross-cultural validity of these questionnaires in patients with NSLBP should be assessed and compared.


The value of preoperative 18F-FDG PET metabolic and volumetric parameters in predicting microvascular invasion and postoperative recurrence of hepatocellular carcinoma.
Microvascular invasion (MVI) is very important in the evaluation of hepatocellular carcinoma (HCC), but diagnosis is determined by postoperative pathology; thus, preoperative noninvasive methods will play an active role. The purpose of the study was to assess the performance of metabolic parameters of preoperative 18F-fluorodeoxyglucose PET/computerized tomography (18F-FDG PET/CT) in the prediction of MVI and postoperative recurrence in primary hepatocellular carcinoma. We retrospectively collected 72 patients with HCC who have performed 18F-FDG PET/CT scan before partial hepatectomy between 2016 and 2019. We used both normal liver tissue and inferior vena cava as the reference background and combined with clinicopathological features, 18F-FDG PET/CT metabolic and volumetric indices to predict MVI and postoperative recurrence of primary HCC before surgery. Twenty-one of the 72 patients recurred, in recurrent cases showed higher maximum standard uptake value (SUVmax), TNR (ratio of tumor SUVmax to mean SUV [SUVmean] of the background tissue), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) than nonrecurrence cases (P < 0.001). All 18F-FDG PET metabolic and volumetric indices for predicting postoperative HCC recurrence were significant on receiver-operating-characteristic (ROC) curve analyses (P < 0.05). TNRIVC, TNRNL, MTVIVC, MTVNL TLGIVC and TLGNL were significant factors for predicting MVI in HCC (P < 0.05). On multivariate analyses, MVI, SUVmax, TNRIVC, TNRNL, MTVIVC, MTVNL, TLGIVC and TLGNL (P < 0.05) are independent risk factors for predicting postoperative HCC recurrence. TNRIVC is the most relevant PET/CT parameter for predicting MVI in HCC, and MTVIVC is the most valuable for predicting postoperative HCC recurrence. Moreover, the PET/CT parameters are more accurate for prognosis with inferior vena cava as a reference background than with normal liver tissue. 18F-FDG PET/CT metabolic and volumetric indices are effective predictors, and could noninvasively provide more comprehensive predictive information on MVI and postoperative recurrence of primary HCC before surgery.


Semantic access in number word translation: the role of crosslingual lexical similarity.
The revised hierarchical model of bilingualism (e.g., Kroll & Stewart, 1994) assumes that second language (L2) words primarily access semantics through their first language (L1) translation equivalents. Consequently, backward translation from L2 to L1 should not imply semantic access but occurs through lexical wordform associations. However, recent research with Dutch-French bilinguals showed that both backward and forward translation of number words yields a semantic number magnitude effect (Duyck & Brysbaert, 2004), providing evidence for strong form-to-meaning mappings of L2 number words. In two number-word translation experiments with Dutch-English-German trilinguals, the present study investigated whether semantic access in L1-L2 and L1-L3 number-word translation depends on lexical similarity of the languages involved. We found that backward translation from these more similar language pairs to L1 still yields a semantic magnitude effect, whereas forward translation does not, in contrast with the Dutch-French results of Duyck and Brysbaert (2004). We argue against a dual route model of word translation and suggest that the degree of semantic activation in translation depends on lexical form overlap between translation equivalents.


Evidence of increased cell proliferation in the hippocampus in children with Ammon's horn sclerosis.
Previous studies of Ammon's horn sclerosis (AHS) suggest that AHS is both the result of and the cause of seizures, and support the idea that seizures cause alterations in cell numbers and location. To test the hypothesis that epilepsy induces neurogenesis/gliogenesis, hippocampal cell proliferation was assessed in AHS. Twelve and four resected hippocampi in patients with AHS and with tumor-related epilepsy (TRE), respectively, and 11 autopsy controls were immunostained for Ki-67. Total number of Ki-67-positive cells (KiPC) in each hippocampal area was counted. Selected cases were further studied with double immunohistochemical labeling. KiPC were observed in all three groups. Total numbers of KiPC were significantly higher in AHS cases than in controls, but were not significantly different between TRE cases and controls. Significant differences were observed in the dentate gyrus, the cornu ammonis (CA)-4 region, and the fissura hippocampi between the AHS and control groups. In double immunolabeling, nestin was positive in some KiPC. The existence of neurogenesis/gliogenesis was shown in the hippocampi of pediatric patients with AHS. Increased numbers of progenitor cells in the hippocampi with AHS appear not to be due to seizures per se, but to be more associated with the specific cause of epilepsy.


Metabolic regulation in bacterial continuous cultures: I.
Dilution rate steps in continuous culture experiments with Klebsiella pneumoniae growing on single substrate feeds have brought out interesting features of metabolic regulation not observed in batch cultures. In a step-up experiment, the adjustment of the culture to a new steady state is preceded by an undershoot in cell density. Results of a step-down experiment indicate a corresponding overshoot phenomenon. These observations of the transient behavior of the culture growing on glucose and xylose as well as the steady-state results are interpreted with cybernetic models. The development of the model explicitly accounts for the lumped internal resource, which is optimally allocated toward the synthesis of key enzymes catalyzing different cellular processes. The model also includes a description of the increased maintenance demand observed at low growth rates. It reduces to previous cybernetic models in situations where the cell does not experience a sudden change in its environment and, hence, retains their predictive capability.


Depletion of dietary arginine inhibits growth of metastatic tumor.
The effects of dietary arginine on the growth of a murine colon tumor metastatic to the liver were examined in a model of advanced neoplastic disease. Tumor growth was influenced by arginine both in vivo and in vitro. An arginine-supplemented diet stimulated tumor growth by 55% compared with controls. Conversely, an arginine-depleted diet inhibited tumor growth by 78% compared with controls. In vitro culture of both murine and human colon tumor cells confirmed that arginine was necessary for cell growth. Flow-cytometric analysis using propidium iodide and bromodeoxyuridine suggested that colon tumor cells cultured without arginine enter a quiescent S phase and depend on arginine for further growth and cell cycle progression. The potential roles for selective dietary arginine modulation in patients with cancer with advanced disease are discussed.


X-chromosome inactivation and evolution in marsupials and other mammals.
Sex chromosome dosage compensation in Australian marsupials exhibits several characteristics not ordinarily manifested in eutherian mammals. They are: 1) preferential inactivation of the paternally derived X-chromosome in somatic tissues; 2) a state of partial inactivity at some paternally derived X-linked gene loci in some cells; 3) absence of dosage compensation in some cell types; 4) absence of nuclear sex dimorphism at interphase; 5) discordance between late DNA replication and gene inactivation in some cell types; 6) failure of the X-chromosome to behave as a single unit. Despite these seemingly major differences between the dosage compensation systems of Australian marsupials and eutherians, there are also many underlying similarities. We propose that the two systems arose from a common ancestral mechanism in which the X-chromosome was regulated in a piecemeal fashion, rather than as a whole. To determine more precisely the sequence and timing of evolutionary events, we have initiated an investigation of dosage compensation in American marsupials, which diverged from Australian marsupials soon after the divergence of marsupials from eutherian mammals.


Slit-Robo signaling.
Slits are secreted proteins that bind to Roundabout (Robo) receptors. Slit-Robo signaling is best known for mediating axon repulsion in the developing nervous system. However, in recent years the functional repertoire of Slits and Robo has expanded tremendously and Slit-Robo signaling has been linked to roles in neurogenesis, angiogenesis and cancer progression among other processes. Likewise, our mechanistic understanding of Slit-Robo signaling has progressed enormously. Here, we summarize new insights into Slit-Robo evolutionary and system-dependent diversity, receptor-ligand interactions, signaling crosstalk and receptor activation.


Characterization of time-dependence for dissipative solitons stabilized by nonlinear gradient terms: Periodic and quasiperiodic vs chaotic behavior.
We investigate the properties of time-dependent dissipative solitons for a cubic complex Ginzburg-Landau equation stabilized by nonlinear gradient terms. The separation of initially nearby trajectories in the asymptotic limit is predominantly used to distinguish qualitatively between time-periodic behavior and chaotic localized states. These results are further corroborated by Fourier transforms and time series. Quasiperiodic behavior is obtained as well, but typically over a fairly narrow range of parameter values. For illustration, two examples of nonlinear gradient terms are examined: the Raman term and combinations of the Raman term with dispersion of the nonlinear gain. For small quintic perturbations, it turns out that the chaotic localized states are showing a transition to periodic states, stationary states, or collapse already for a small magnitude of the quintic perturbations. This result indicates that the basin of attraction for chaotic localized states is rather shallow.


Dermoscopic Criteria, Histopathological Correlates and Genetic Findings of Thin Melanoma on Non-Volar Skin.
Dermoscopy is a non-invasive, in vivo technique that allows the visualization of subsurface skin structures in the epidermis, at the dermoepidermal junction, and in the upper dermis. Dermoscopy brought a new dimension in evaluating melanocytic skin neoplasms (MSN) also representing a link between clinical and pathologic examination of any MSN. However, histopathology remains the gold standard in diagnosing MSN. Dermoscopic-pathologic correlation enhances the level of quality of MSN diagnosis and increases the level of confidence of pathologists. Melanoma is one of the most genetically predisposed among all cancers in humans. The genetic landscape of melanoma has been described in the last years but is still a field in continuous evolution. Melanoma genetic markers play a role not only in melanoma susceptibility, initiation, and progression but also in prognosis and therapeutic decisions. Several studies described the dermoscopic specific criteria and predictors for melanoma and their histopathologic correlates, but only a few studies investigated the correlation among dermoscopy, pathology, and genetic of MSN. The aim of this work is to review the published data about dermoscopic features of melanoma, their histopathological correlates with regards also to genetic alterations. Particularly, this review will focus on low-CSD (cumulative sun damage) melanoma or superficial spreading melanoma, high-CSD melanoma, and nevus-associated melanoma.


Analysis of hospital costs as a basis for pricing services in Mali.
In a move to achieve a better equity in the funding of access to health care, particularly for the poor, a better efficiency of hospital functioning and a better financial balance, the analysis of hospital costs in Mali brings several key elements to improve the pricing of medical services. The method utilized is the classical step-down process which takes into consideration the entire set of direct and indirect costs borne by the hospital. Although this approach does not allow to estimate the economic cost of consultations, it is a useful contribution to assess the financial activity of the hospital and improve its performance, financially speaking, through a more relevant user fees policy. The study shows that there are possibilities of cross-subsidies within the hospital or within services which improve the recovery of some of the current costs. It also leads to several proposals of pricing care while taking into account the constraints, the level of the hospital its specific conditions and equity.


Early exposures and inherent factors in premature newborns are associated with type 1 diabetes.
Pathophysiology of type 1 diabetes (T1D) involves immune responses that may be associated with early exposure to environmental factors among preterm newborns. The aim of this work was to evaluate for association between T1D and maternal, nutritional, and medical exposures during the neonatal period among premature newborns. This is a multicenter, matched case-control study. Preterm newborns, who developed T1D before 18 years, were matched by sex, gestational age (GA), birth date, and medical center of birth with newborns who did not develop TID. Data included maternal medical history, birth weight (BW), length of hospitalization, enteral and parenteral medications, fluid administration, and feeding modalities during hospitalization. Fifty-two patients with T1D, 26 males, median age at T1D diagnosis 8.17 years (5.92-9.77), median GA 34 weeks (33-m36), and 132 matched controls, were included. Multivariate-conditional-regression demonstrated a significant association between T1D and any maternal illness (23.1% vs. 9.1%, OR = 4.99 (1.69-14.72), p = 0.004), higher BW-SDS (0.07 ± 0.95 vs. -0.27 ± 0.97, OR = 2.03 (1.19-3.49), p = 0.01), longer duration of glucose infusion (3 (1-5) days vs. 2 (0-4), OR = 1.23 (1.03-1.46), p = 0.02), and antibiotic therapy beyond the first week of life (19.2% vs. 6.9%, OR = 5.22 (1.32-20.70), p = 0.019). Antibiotic treatment during the first week of life was negatively associated with T1D (51.9% vs. 67.2%, OR 0.31 (0.11-0.88), p = 0.027). A novel association was demonstrated between the development of T1D and early interventions and exposures among preterm newborns. Type 1 diabetes mellitus during childhood may be associated with early exposures during the neonatal period, in addition to known maternal and neonatal metabolic parameters. Early exposure to intravenous antibiotics, differing between the first week of life and later, and longer parenteral glucose administration to preterm newborns were associated with childhood type 1 diabetes. This is in addition to familiar maternal risk factors. Future prospective studies should examine the microbial changes and immune system characteristics of preterm and term neonates exposed to parenteral antibiotics and glucose treatment, in order to validate our exploratory findings.


Early-life Programming of Type 2 Diabetes Mellitus: Understanding the Association between Epigenetics/Genetics and Environmental Factors.
Type 2 Diabetes Mellitus is an increasing public health problem that poses a severe social and economic burden affecting both developed and developing countries. Defects in insulin signaling itself are among the earliest indications that an individual is predisposed to the development of insulin resistance and subsequently Type 2 Diabetes Mellitus. To date, however, the underlying molecular mechanisms which result in resistance to the actions of insulin are poorly understood. Furthermore, it has been shown that maternal obesity is associated with an increased risk of obesity and insulin resistance in the offspring. However, the genetic and/or epigenetic modifications within insulin-sensitive tissues such as the liver and skeletal muscle, which contribute to the insulin-resistant phenotype, still remain unknown. More importantly, a lack of in-depth understanding of how the early life environment can have long-lasting effects on health and increased risk of Type 2 Diabetes Mellitus in adulthood poses a major limitation to such efforts. The focus of the current review is thus to discuss recent experimental and human evidence of an epigenetic component associated with components of nutritional programming of Type 2 Diabetes Mellitus, including altered feeding behavior, adipose tissue, and pancreatic beta-cell dysfunction, and transgenerational risk transmission.


Drug discovery targeting Chk1 and Chk2 kinases.
The DNA damage response includes not only checkpoint and apoptosis, but also direct activation of DNA repair networks. Downstream in the DNA damage response pathway are Chk1, an essential checkpoint kinase, and Chk2, which plays a critical role in p53-dependent apoptosis. Chk1 inhibition is expected to lead to chemosensitization of tumors, while Chk2 inhibition could protect normal sensitive tissues from some chemotherapeutic agents. Drugs targeting Chk1 and Chk2 have the potential to significantly improve the therapeutic window of DNA damaging agents available in the clinic.


An autoregulatory feedback loop involving PAP1 and TAS4 in response to sugars in Arabidopsis.
miR828 in Arabidopsis triggers the cleavage of Trans-Acting SiRNA Gene 4 (TAS4) transcripts and production of small interfering RNAs (ta-siRNAs). One siRNA, TAS4-siRNA81(-), targets a set of MYB transcription factors including PAP1, PAP2, and MYB113 which regulate the anthocyanin biosynthesis pathway. Interestingly, miR828 also targets MYB113, suggesting a close relationship between these MYBs, miR828, and TAS4, but their evolutionary origins are unknown. We found that PAP1, PAP2, and TAS4 expression is induced specifically by exogenous treatment with sucrose and glucose in seedlings. The induction is attenuated in abscisic acid (ABA) pathway mutants, especially in abi3-1 and abi5-1 for PAP1 or PAP2, while no such effect is observed for TAS4. PAP1 is under regulation by TAS4, demonstrated by the accumulation of PAP1 transcripts and anthocyanin in ta-siRNA biogenesis pathway mutants. TAS4-siR81(-) expression is induced by physiological concentrations of Suc and Glc and in pap1-D, an activation-tagged line, indicating a feedback regulatory loop exists between PAP1 and TAS4. Bioinformatic analysis revealed MIR828 homologues in dicots and gymnosperms, but only in one basal monocot, whereas TAS4 is only found in dicots. Consistent with this observation, PAP1, PAP2, and MYB113 dicot paralogs show peptide and nucleotide footprints for the TAS4-siR81(-) binding site, providing evidence for purifying selection in contrast to monocots. Extended sequence similarities between MIR828, MYBs, and TAS4 support an inverted duplication model for the evolution of MIR828 from an ancestral gymnosperm MYB gene and subsequent formation of TAS4 by duplication of the miR828* arm. We obtained evidence by modified 5'-RACE for a MYB mRNA cleavage product guided by miR828 in Pinus resinosa. Taken together, our results suggest that regulation of anthocyanin biosynthesis by TAS4 and miR828 in higher plants is evolutionarily significant and consistent with the evolution of TAS4 since the dicot-monocot divergence.


Gas bubble pulsation in a semiconfined space subjected to ultrasound.
In the case of ultrasound application in biological tissues, gas bubbles might form and collapse within cells, in the intercellular spaces and on tissue surfaces. In this work the effect of confined space on the behavior of the gas bubble in the presence of ultrasonic field is studied. A numerical model for bubble pulsation in a planar liquid layer, bounded by two rigid walls, is developed. Surface tension at the interface between the host liquid and the gas in the bubble is considered as well. A mathematical statement and solution technique based on the boundary integral method are presented. In some cases, the bubble divides into two symmetrical parts and high-velocity jets are generated, aimed at the walls. The final velocity of the jets strongly depends on the surface tension of the host liquid. Two new parameters that predict the occurrence of jet formation are developed.


How to inhibit telomerase activity for cancer therapy.
Telomerase is a target for anticancer research because telomerase activity is closely correlated with malignancy. Inhibition of telomerase activity should increase telomere shortening, which destabilizes chromosomes, thus leading to cellular senescence and death. Extensive investigations have addressed the molecular mechanisms of telomerase activation in cancers. Based on results from these studies, various attempts have been made to inhibit telomerase activity using molecular techniques in cancer cells. Antisense oligonucleotides directed to human telomerase RNA, the dominant negative form of human telomerase reverse transcriptase (hTERT), hammerhead ribozymes that cut hTR and agents that interact with quadruplex DNA represent potential telomerase inhibitors. This review includes a summary of recent attempts to inhibit telomerase activity in cancer cells and a discussion of how these tools can be applied to cancer therapy, especially in combination with established anti-cancer agents.


Clinical advances in immunotherapy for immune-mediated glomerular diseases.
Due to the suboptimal therapeutic efficacy and potential adverse effects associated with traditional immunosuppressive medications, there has been an increasing emphasis on the development and utilization of immunotherapies. This paper aims to provide clinicians with valuable insights for selecting appropriate therapeutic approaches and contribute to the development of novel immunotherapeutic drugs. This paper categorizes the immunotherapeutic drugs that are used for the treatment of immune-mediated glomerular diseases into three groups: immunotherapies targeting antigen-presenting cells (anti-CD80), immunotherapies targeting T/B cells (anti-CD20, anti-CD22, BAFF and APRIL inhibitors, CD40-CD40L inhibitors, proteasome inhibitors, Syk inhibitors, and Btk inhibitors), and immunotherapies targeting the complement system (C5 inhibitors, C5a/C5aR inhibitors, C3 inhibitors, MASP2 inhibitors, factor B inhibitors, and factor D inhibitors). The article then provides a comprehensive overview of advances related to these immunotherapeutic drugs in clinical research. Certain immunotherapeutic drugs, such as rituximab, belimumab, and eculizumab, have exhibited notable efficacy in treating specific immune-mediated glomerular diseases, thereby providing novel therapeutic approaches for patients. Nonetheless, the efficacy of numerous immunotherapeutic drugs remains to be substantiated.


Expression of activating transcription factor 5 (ATF5) is increased in astrocytomas of different WHO grades and correlates with survival of glioblastoma patients.
ATF5 suppresses differentiation of neuroprogenitor cells and is overexpressed in glioblastoma (GBM). A reduction of its expression leads to apoptotic GBM cell death. Data on ATF5 expression in astrocytoma WHO grade II (low-grade astrocytoma [LGA]) are scarce and lacking on recurrent GBM. ATF5 mRNA was extracted from frozen samples of patients' GBM (n=79), LGA (n=40), and normal brain (NB, n=10), quantified by duplex qPCR and correlated with retrospectively collected clinical data. ATF5 protein expression was evaluated by measuring staining intensity on immunohistochemistry. ATF5 mRNA was overexpressed in LGA (sevenfold, P<0.001) and GBM (tenfold, P<0.001) compared to NB, which was confirmed on protein level. Although ATF5 mRNA expression in GBM showed a considerable fluctuation range, groups of varying biological behavior, that is, local/multifocal growth or primary tumor/relapse and the tumor localization at diagnosis, were not significantly different. ATF5 mRNA correlated with the patients' age (r=0.339, P=0.028) and inversely with Ki67-staining (r=-0.421, P=0.007). GBM patients were allocated to a low and a high ATF5 expression group by the median ATF5 overexpression compared to NB. Kaplan-Meier analysis and Cox regression indicated that ATF5 mRNA expression significantly correlated with short-term survival (t,12 months, median survival 18 vs 13 months, P=0.022, HR 2.827) and progression-free survival (PFS) (12 vs 6 months, P=0.024). This advantage vanished after 24 months (P=0.084). ATF5 mRNA expression could be identified as an additional, though not independent factor correlating with overall survival and PFS. Since its inhibition might lead to the selective death of glioma cells, it might serve as a potential ubiquitous therapeutic target in astrocytic tumors.


A conserved mechanism for mitochondria-dependent dynein anchoring.
Mitochondrial anchors have functions that extend beyond simply positioning mitochondria. In budding yeast, mitochondria drive the assembly of the mitochondrial anchor protein Num1 into clusters, which serve to anchor mitochondria as well as dynein to the cell cortex. Here, we explore a conserved role for mitochondria in dynein anchoring by examining the tethering functions of the evolutionarily distant Schizosaccharomyces pombe Num1 homologue. In addition to its function in dynein anchoring, we find that S. pombe Num1, also known as Mcp5, interacts with and tethers mitochondria to the plasma membrane in S. pombe and Saccharomyces cerevisiae. Thus, the mitochondria and plasma membrane-binding domains of the Num1 homologues, as well as the membrane features these domains recognize, are conserved. In S. pombe, we find that mitochondria impact the assembly and cellular distribution of Num1 clusters and that Num1 clusters actively engaged in mitochondrial tethering serve as cortical attachment sites for dynein. Thus, mitochondria play a critical and conserved role in the formation and distribution of dynein-anchoring sites at the cell cortex and, as a consequence, impact dynein function. These findings shed light on an ancient mechanism of mitochondria-dependent dynein anchoring that is conserved over more than 450 million years of evolution, raising the intriguing possibility that the role mitochondria play in dynein anchoring and function extends beyond yeast to higher eukaryotes.


Canada's national initiative to advance access to electronic journals.
This paper describes a national experiment in the licensing of full text information in journals, primarily in the fields of science, technology and medicine. It discusses the initiative of the federal government of Canada through the creation of the Canada Foundation for Innovation as a new funding agency, with an objective of improving research and creativity in Canadian science. The successful efforts initiated by the Canadian Association of Research Libraries/Association des bibliothèques de recherche du Canada to create a funding opportunity to develop the 'information infrastructure' for Canadian researchers and the resulting Canadian National Site Licensing Project (CNSLP) progress is discussed. The evolution of a project governance structure to maintain the support of the 64 participating institutions is reviewed and the need to develop an appropriate exit strategy at the conclusion of the federal funding is also considered.


Convergent Evolution of Cichlid Fish Pharyngeal Jaw Dentitions in Mollusk-Crushing Predators: Comparative X-Ray Computed Tomography of Tooth Sizes, Numbers, and Replacement.
Dental convergence is a hallmark of cichlid fish adaptive radiations. This type of repeated evolution characterizes both the oral jaws of these fishes as well as their pharyngeal jaws that are modified gill arches used to functionally process prey like hard-shelled mollusks. To test several hypotheses regarding the evolution of cichlid crushing pharyngeal dentitions, we used X-ray computed tomography scans to comparatively examine dental evolution in the pharyngeal jaw of a diversity of New World Heroine cichlid lineages. The substantial variation in erupted tooth sizes and numbers as well as replacement teeth found in these fishes showed several general patterns. Larger toothed species tended to have fewer teeth suggesting a potential role of spatial constraints in cichlid dental divergence. Species with larger numbers of erupted pharyngeal teeth also had larger numbers of replacement teeth. Replacement tooth size is almost exactly predicted (r = 0.99) from the size of erupted teeth across all of the species. Mollusk crushing was, therefore, highly associated with not only larger pharyngeal teeth, but also larger replacement teeth. Whether dental divergence arises as a result of environmental induced plasticity or originates via trophic polymorphism as found in the species Herichthys minckleyi, there appear to be general rules that structure interspecific divergence in cichlid pharyngeal erupted and replacement dentitions.


Independent stimulation of glucose metabolism and Na+-K+ exchange by insulin in the human forearm.
Insulin promotes potassium uptake into skeletal muscle by stimulating the activity of the Na+-K+ pump. To test whether insulin-induced glucose and potassium uptake are linked processes in vivo, we used the perfused forearm technique in healthy volunteers. Local hyperinsulinemia (125 +/- 11 microU/ml for 100 min) induced a net uptake of glucose and potassium (4.79 +/- 0.61 and 0.76 +/- 0.22 mumol.min-1.100 ml-1 of forearm volume, respectively). When an intra-arterial ouabain infusion (0.72 microgram.min-1.100 ml-1, producing local levels of approximately 0.5 mM) was superimposed on the insulin infusion, potassium uptake was blocked (0.026 +/- 0.190 ml.min-1.100 ml-1, P less than 0.02), and glucose uptake was decreased (to 3.31 +/- 0.34 mumol.min-1.100 ml-1, P less than 0.03). The latter change was explained by a 30% fall in forearm blood flow (from 2.95 +/- 0.10 to 2.01 +/- 0.18 ml.min-1.100 ml-1, P less than 0.001). To separate out the effect of blood flow, in another series of studies forearm blood flow was clamped by co-infusing propranolol and phentolamine (7 and 8 micrograms.min-1.100 ml-1, respectively). Under these conditions of fixed flow (7.0 +/- 0.8 ml.min-1.100 ml-1), ouabain still abolished the stimulatory effect of insulin on potassium uptake but had only a small (and statistically insignificant) effect on forearm glucose extraction (from 20 +/- 2 to 16 +/- 2%, P = N>). We conclude that in human forearm muscle ouabain inhibits Na+-K+ exchange and depresses insulin-induced glucose uptake via an adrenergic-mediated limitation of blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of ginsenoside Rb1 on oxidative stress injury in rat spinal cords by regulating the eNOS/Nrf2/HO-1 signaling pathway.
The present study aimed to investigate whether ginsenoside Rb1 (G-Rb1) attenuates spinal cord injury-associated oxidative stress in rats by regulating the endothelial nitric oxide synthase eNOS/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 signaling pathway. Sprague Dawley rats were randomly divided into the sham operation group (S group), spinal cord injury group (SCI group), G-Rb1 treatment group (G-Rb1 group) and SCI+G-Rb1+Inhibitor L-name group (L-name group). The posterior limb function was evaluated via the Basso, Beattie and Bresnahan scoring method. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) in serum were measured by ELISA. The pathological changes in the spinal cord were observed by H&E staining. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to detect eNOS, phosphorylated (p)-eNOS, heat shock protein (HSP)90, Nrf2 and NAD(P)H quinone dehydrogenase 1 (Nqo1) at the mRNA and protein level. Immunohistochemistry was used to detect the expression of Nrf2 and p-eNOS. Compared with the S group, the scores of spinal cord function in the SCI group were significantly lower, and the levels of MDA were significantly increased, while the levels of SOD, CAT and GSH protein in spinal cord were significantly decreased (P<0.05). The spinal cord tissue exhibited hemorrhage, neuronal degeneration/necrosis, as well as mononuclear cell and lymphocyte infiltration. The eNOS, HSP90, Nrf2, Nqo1 and HO-1 mRNA levels were decreased (P<0.05). Compared with those in the SCI group, the spinal cord function score in the G-Rb1 group were significantly higher and the serum MDA content was significantly decreased, while the activity of SOD, CAT and GSH was significantly increased (P<0.05). The degeneration/necrosis of spinal cord neurons was attenuated, inflammatory cell infiltration was significantly reduced and the levels of eNOS, HSP90, Nrf2, Nqo1 and HO-1 were significantly upregulated (P<0.05). In the group that was administered the eNOS inhibitor L-name, the levels of eNOS, HSP90, Nrf2, Nqo1 and HO-1 were significantly decreased. In conclusion, G-Rb1 attenuates oxidative stress in injured spinal cords. The mechanism may at least in part involve the eNOS/Nrf2/HO-1 pathway.


A novel all-in-one conditional knockout system uncovered an essential role of DDX1 in ribosomal RNA processing.
Generation of conditional knockout (cKO) and various gene-modified cells is laborious and time-consuming. Here, we established an all-in-one cKO system, which enables highly efficient generation of cKO cells and simultaneous gene modifications, including epitope tagging and reporter gene knock-in. We applied this system to mouse embryonic stem cells (ESCs) and generated RNA helicase Ddx1 cKO ESCs. The targeted cells displayed endogenous promoter-driven EGFP and FLAG-tagged DDX1 expression, and they were converted to Ddx1 KO via FLP recombinase. We further established TetFE ESCs, which carried a reverse tetracycline transactivator (rtTA) expression cassette and a tetracycline response element (TRE)-regulated FLPERT2 cassette in the Gt(ROSA26)Sor locus for instant and tightly regulated induction of gene KO. By utilizing TetFE Ddx1F/F ESCs, we isolated highly pure Ddx1F/F and Ddx1-/- ESCs and found that loss of Ddx1 caused rRNA processing defects, thereby activating the ribosome stress-p53 pathway. We also demonstrated cKO of various genes in ESCs and homologous recombination-non-proficient human HT1080 cells. The frequency of cKO clones was remarkably high for both cell types and reached up to 96% when EGFP-positive clones were analyzed. This all-in-one cKO system will be a powerful tool for rapid and precise analyses of gene functions.


Spatial variation in the bacterial and denitrifying bacterial community in a biofilter treating subsurface agricultural drainage.
Denitrifying biofilters can remove agricultural nitrates from subsurface drainage, reducing nitrate pollution that contributes to coastal hypoxic zones. The performance and reliability of natural and engineered systems dependent upon microbially mediated processes, such as the denitrifying biofilters, can be affected by the spatial structure of their microbial communities. Furthermore, our understanding of the relationship between microbial community composition and function is influenced by the spatial distribution of samples.In this study we characterized the spatial structure of bacterial communities in a denitrifying biofilter in central Illinois. Bacterial communities were assessed using automated ribosomal intergenic spacer analysis for bacteria and terminal restriction fragment length polymorphism of nosZ for denitrifying bacteria.Non-metric multidimensional scaling and analysis of similarity (ANOSIM) analyses indicated that bacteria showed statistically significant spatial structure by depth and transect,while denitrifying bacteria did not exhibit significant spatial structure. For determination of spatial patterns, we developed a package of automated functions for the R statistical environment that allows directional analysis of microbial community composition data using either ANOSIM or Mantel statistics.Applying this package to the biofilter data, the flow path correlation range for the bacterial community was 6.4 m at the shallower, periodically in undated depth and 10.7 m at the deeper, continually submerged depth. These spatial structures suggest a strong influence of hydrology on the microbial community composition in these denitrifying biofilters. Understanding such spatial structure can also guide optimal sample collection strategies for microbial community analyses.


A cross-sectional examination of marketing of electronic cigarettes on Twitter.
Rapid increases in marketing of e-cigarettes coincide with growth in e-cigarette use in recent years; however, little is known about how e-cigarettes are marketed on social media platforms. Keywords were used to collect tweets related to e-cigarettes from the Twitter Firehose between 1 May 2012 and 30 June 2012. Tweets were coded for smoking cessation mentions, as well as health and safety mentions, and were classified as commercial or non-commercial ('organic') tweets using a combination of Naïve Bayes machine learning methods, keyword algorithms and human coding. Metadata associated with each tweet were used to examine the characteristics of accounts tweeting about e-cigarettes. 73,672 tweets related to e-cigarettes were captured in the study period, 90% of which were classified as commercial tweets. Accounts tweeting commercial e-cigarette content were associated with lower Klout scores, a measure of influence. Commercial tweeting was largely driven by a small group of highly active accounts, and 94% of commercial tweets included links to websites, many of which sell or promote e-cigarettes. Approximately 10% of commercial and organic tweets mentioned smoking cessation, and 34% of commercial tweets included mentions of prices or discounts for e-cigarettes. Twitter appears to be an important marketing platform for e-cigarettes. Tweets related to e-cigarettes were overwhelmingly commercial, and a substantial proportion mentioned smoking cessation. E-cigarette marketing on Twitter may have public health implications. Continued surveillance of e-cigarette marketing on social media platforms is needed.


Multiplex quantitative analysis of eicosanoid mediators in human plasma and serum: Possible introduction into clinical testing.
Eicosanoid mediators play important roles in maintaining the physiological and pathophysiological homeostasis in the body. Their measurements, however, are rarely performed in clinical practice. In the present study, we analyzed 30 varieties of eicosanoid mediators that were detectable in human plasma and serum collected from healthy donors, using liquid chromatography-tandem mass spectrometry from the viewpoint of the clinical application of the multiplex quantitation of eicosanoid mediators. Wider variety of eicosanoid mediators were detected in serum (27 out of 30) than in plasma (14 out of 30), since the serum was thought to contain lipid mediators released from activated platelets. Larger inter-individual variations were observed in the plasma and serum eicosanoid levels. On the other hand, the concentrations of eicosanoids were not affected by the platelet count but were affected by the concentration of arachidonic acid (AA) within the reference interval (17.4-40.5×1010/L). When serum samples from patients with hematological disorders were analyzed, the concentrations of AA were positively correlated with the platelet count. When the patients underwent ASA therapy, a marked decrease in the concentrations of thromboxane B2 (TXB2) and 12-hydroxyl-heptadecatrienoic acid (12-HHT) was observed. Considering the availability of serum samples in clinical settings, the serum analysis of eicosanoids may be clinically useful.


Differences in the neurochemical and behavioural profiles of lisdexamfetamine methylphenidate and modafinil revealed by simultaneous dual-probe microdialysis and locomotor activity measurements in freely-moving rats.
Lisdexamfetamine dimesylate is a novel prodrug approved in North America, Europe and Brazil for treating attention deficit hyperactivity disorder (ADHD). It undergoes rate-limited hydrolysis by red blood cells to yield d-amphetamine. Following our previous work comparing lisdexamfetamine with d-amphetamine, the neurochemical and behavioural profiles of lisdexamfetamine, methylphenidate and modafinil were compared by dual-probe microdialysis in the prefrontal cortex (PFC) and striatum of conscious rats with simultaneous locomotor activity measurement. We employed pharmacologically equivalent doses of all compounds and those that spanned the therapeutically relevant and psychostimulant range. Lisdexamfetamine (0.5, 1.5, 4.5 mg/kg d-amphetamine base, per os (po)), methylphenidate (3, 10, 30 mg/kg base, po) and modafinil (100, 300, 600 mg/kg base, po) increased efflux of dopamine and noradrenaline in PFC, and dopamine in striatum. Only lisdexamfetamine increased 5-hydroxytryptamine (5-HT) efflux in PFC and striatum. Lisdexamfetamine had larger and more sustained effects on catecholaminergic neurotransmission than methylphenidate or modafinil. Linear correlations were observed between striatal dopamine efflux and locomotor activity for lisdexamfetamine and methylphenidate, but not modafinil. Regression slopes revealed greater increases in extracellular dopamine could be elicited without producing locomotor activation by lisdexamfetamine than methylphenidate. These results are consistent with clinical findings showing that lisdexamfetamine is an effective ADHD medication with prolonged duration of action and good separation between its therapeutic actions and stimulant side-effects.


Transport and fate of silver as polymer-stabilised nanoparticles and ions in a pilot wastewater treatment plant, followed by sludge digestion and disposal of sludge/soil mixtures: A case study.
A case study of transport and changes in properties of polymer-stabilised Ag NPs is presented in this paper investigating their interaction in different treatment steps within a fully realistic pilot wastewater treatment plant (WWTP), in anaerobic digested sludge, and in soil/sludge mixtures. The fate of the same Ag NPs was tracked in these environments, hence taking the history of the Ag NPs into account. The results show that most of the Ag NPs end up in the sludge (80-100%), also after anaerobically digestion. Furthermore, the fraction of silver in the supernatant was very low after 48 h incubation with silver-containing digested sludge mixed with different soil types. However, when Ag NPs were added directly to the sludge/soil mixture, soluble silver was present in the supernatant with sandy soil, but not with clayey soil. In all, generated findings show that risk assessments and toxicological studies of Ag NPs suspensions must take into account possible chemical and particle transformations upon environmental entry, as silver in general become less soluble when transported to WWTPs and interacting with sludge, and soil.