Would loss to follow-up bias the outcome evaluation of patients operated for degenerative disorders of the lumbar spine?: A study of responding and non-responding cohort participants from a clinical spine surgery registry

Loss to follow-up may bias the outcome assessments of clinical registries. In this study, we wanted to determine whether outcomes were different in responding and non-responding patients who were included in a clinical spine surgery registry, at two years of follow-up. In addition, we wanted to identify risk factors for failure to respond. 633 patients who were operated for degenerative disorders of the lumbar spine were followed for 2 years using a local clinical spine registry. Those who did not attend the clinic and those who did not answer a postal questionnaire—for whom 2 years of outcome data were missing—and who would be lost to follow-up according to the standard procedures of the registry protocols, were defined as non-respondents. They were traced and interviewed by telephone. Outcome measures were: improvement in health-related quality of life (EQ-5D), leg pain, and back pain; and also general state of health, employment status, and perceived benefits of the operation. We found no statistically significant differences in outcome between respondents (78% of the patients) and nonrespondents (22%). Receipt of postal questionnaires (not being summoned for a follow-up visit) was the strongest risk factor for failure to respond. Forgetfulness appeared to be an important cause. Older patients and those who had complications were more likely to respond. Interpretation A loss to follow-up of 22% would not bias conclusions about overall treatment effects and, importantly, there were no indications of worse outcomes in non-respondents

Inhibition of Biofilm Formation, Quorum Sensing and Infection in Pseudomonas aeruginosa by Natural Products-Inspired Organosulfur Compounds

Using a microplate-based screening assay, the effects on Pseudomonas aeruginosa PAO1 biofilm formation of several S-substituted cysteine sulfoxides and their corresponding disulfide derivatives were evaluated. From our library of compounds, S-phenyl-L-cysteine sulfoxide and its breakdown product, diphenyl disulfide, significantly reduced the amount of biofilm formation by P. aeruginosa at levels equivalent to the active concentration of 4-nitropyridine-N-oxide (NPO) (1 mM). Unlike NPO, which is an established inhibitor of bacterial biofilms, our active compounds did not reduce planktonic cell growth and only affected biofilm formation. When used in a Drosophila-based infection model, both S-phenyl-L-cysteine sulfoxide and diphenyl disulfide significantly reduced the P. aeruginosa recovered 18 h post infection (relative to the control), and were non-lethal to the fly hosts. The possibility that the observed biofilm inhibitory effects were related to quorum sensing inhibition (QSI) was investigated using Escherichia coli-based reporters expressing P. aeruginosa lasR or rhIR response proteins, as well as an endogenous P. aeruginosa reporter from the lasI/lasR QS system. Inhibition of quorum sensing by S-phenyl-L-cysteine sulfoxide was observed in all of the reporter systems tested, whereas diphenyl disulfide did not exhibit QSI in either of the E. coli reporters, and showed very limited inhibition in the P. aeruginosa reporter. Since both compounds inhibit biofilm formation but do not show similar QSI activity, it is concluded that they may be functioning by different pathways. The hypothesis that biofilm inhibition by the two active compounds discovered in this work occurs through QSI is discussed

The Role of Anorexia in Resistance and Tolerance to Infections in Drosophila

Infections initiate a signaling loop in which sick animals become anorexic, and the resulting change in diet alters the body's ability to fight infections in good and bad ways

Maternal characteristics associated with the dietary intake of nitrates, nitrites, and nitrosamines in women of child-bearing age: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Multiple <it>N</it>-nitroso compounds have been observed in animal studies to be both mutagenic and teratogenic. Human exposure to <it>N</it>-nitroso compounds and their precursors, nitrates and nitrites, can occur through exogenous sources, such as diet, drinking water, occupation, or environmental exposures, and through endogenous exposures resulting from the formation of <it>N</it>-nitroso compounds in the body. Very little information is available on intake of nitrates, nitrites, and nitrosamines and factors related to increased consumption of these compounds.</p> <p>Methods</p> <p>Using survey and dietary intake information from control women (with deliveries of live births without major congenital malformations during 1997-2004) who participated in the National Birth Defects Prevention Study (NBDPS), we examined the relation between various maternal characteristics and intake of nitrates, nitrites, and nitrosamines from dietary sources. Estimated intake of these compounds was obtained from the Willet Food Frequency Questionnaire as adapted for the NBDPS. Multinomial logistic regression models were used to estimate odds ratios and 95% confidence intervals for the consumption of these compounds by self-reported race/ethnicity and other maternal characteristics.</p> <p>Results</p> <p>Median intake per day for nitrates, nitrites, total nitrites (nitrites + 5% nitrates), and nitrosamines was estimated at 40.48 mg, 1.53 mg, 3.69 mg, and 0.472 μg respectively. With the lowest quartile of intake as the referent category and controlling for daily caloric intake, factors predicting intake of these compounds included maternal race/ethnicity, education, body mass index, household income, area of residence, folate intake, and percent of daily calories from dietary fat. Non-Hispanic White participants were less likely to consume nitrates, nitrites, and total nitrites per day, but more likely to consume dietary nitrosamines than other participants that participated in the NBDPS. Primary food sources of these compounds also varied by maternal race/ethnicity.</p> <p>Conclusions</p> <p>Results of this study indicate that intake of nitrates, nitrites, and nitrosamines vary considerably by race/ethnicity, education, body mass index, and other characteristics. Further research is needed regarding how consumption of foods high in nitrosamines and <it>N</it>-nitroso precursors might relate to risk of adverse pregnancy outcomes and chronic diseases.</p

The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence

Trost E, Ott L, Schneider J, et al. The complete genome sequence of Corynebacterium pseudotuberculosis FRC41 isolated from a 12-year-old girl with necrotizing lymphadenitis reveals insights into gene-regulatory networks contributing to virulence. BMC Genomics. 2010;11(1): 728

Functional Characterisation and Drug Target Validation of a Mitotic Kinesin-13 in Trypanosoma brucei

Mitotic kinesins are essential for faithful chromosome segregation and cell proliferation. Therefore, in humans, kinesin motor proteins have been identified as anti-cancer drug targets and small molecule inhibitors are now tested in clinical studies. Phylogenetic analyses have assigned five of the approximately fifty kinesin motor proteins coded by Trypanosoma brucei genome to the Kinesin-13 family. Kinesins of this family have unusual biochemical properties because they do not transport cargo along microtubules but are able to depolymerise microtubules at their ends, therefore contributing to the regulation of microtubule length. In other eukaryotic genomes sequenced to date, only between one and three Kinesin-13s are present. We have used immunolocalisation, RNAi-mediated protein depletion, biochemical in vitro assays and a mouse model of infection to study the single mitotic Kinesin-13 in T. brucei. Subcellular localisation of all five T. brucei Kinesin-13s revealed distinct distributions, indicating that the expansion of this kinesin family in kinetoplastids is accompanied by functional diversification. Only a single kinesin (TbKif13-1) has a nuclear localisation. Using active, recombinant TbKif13-1 in in vitro assays we experimentally confirm the depolymerising properties of this kinesin. We analyse the biological function of TbKif13-1 by RNAi-mediated protein depletion and show its central role in regulating spindle assembly during mitosis. Absence of the protein leads to abnormally long and bent mitotic spindles, causing chromosome mis-segregation and cell death. RNAi-depletion in a mouse model of infection completely prevents infection with the parasite. Given its essential role in mitosis, proliferation and survival of the parasite and the availability of a simple in vitro activity assay, TbKif13-1 has been identified as an excellent potential drug target

Supersymmetric QCD corrections to e+e−→tbˉH−e^+e^-\to t\bar{b}H^- and the Bernstein-Tkachov method of loop integration

The discovery of charged Higgs bosons is of particular importance, since their existence is predicted by supersymmetry and they are absent in the Standard Model (SM). If the charged Higgs bosons are too heavy to be produced in pairs at future linear colliders, single production associated with a top and a bottom quark is enhanced in parts of the parameter space. We present the next-to-leading-order calculation in supersymmetric QCD within the minimal supersymmetric SM (MSSM), completing a previous calculation of the SM-QCD corrections. In addition to the usual approach to perform the loop integration analytically, we apply a numerical approach based on the Bernstein-Tkachov theorem. In this framework, we avoid some of the generic problems connected with the analytical method.Comment: 14 pages, 6 figures, accepted for publication in Phys. Rev.

Tracking of an electron beam through the solar corona with LOFAR

© ESO 2018. The Sun's activity leads to bursts of radio emission, among other phenomena. An example is type-III radio bursts. They occur frequently and appear as short-lived structures rapidly drifting from high to low frequencies in dynamic radio spectra. They are usually interpreted as signatures of beams of energetic electrons propagating along coronal magnetic field lines. Here we present novel interferometric LOFAR (LOw Frequency ARray) observations of three solar type-III radio bursts and their reverse bursts with high spectral, spatial, and temporal resolution. They are consistent with a propagation of the radio sources along the coronal magnetic field lines with nonuniform speed. Hence, the type-III radio bursts cannot be generated by a monoenergetic electron beam, but by an ensemble of energetic electrons with a spread distribution in velocity and energy. Additionally, the density profile along the propagation path is derived in the corona. It agrees well with three-fold coronal density model by (1961, ApJ, 133, 983)

Comparative Analysis of Acinetobacters: Three Genomes for Three Lifestyles

Acinetobacter baumannii is the source of numerous nosocomial infections in humans and therefore deserves close attention as multidrug or even pandrug resistant strains are increasingly being identified worldwide. Here we report the comparison of two newly sequenced genomes of A. baumannii. The human isolate A. baumannii AYE is multidrug resistant whereas strain SDF, which was isolated from body lice, is antibiotic susceptible. As reference for comparison in this analysis, the genome of the soil-living bacterium A. baylyi strain ADP1 was used. The most interesting dissimilarities we observed were that i) whereas strain AYE and A. baylyi genomes harbored very few Insertion Sequence elements which could promote expression of downstream genes, strain SDF sequence contains several hundred of them that have played a crucial role in its genome reduction (gene disruptions and simple DNA loss); ii) strain SDF has low catabolic capacities compared to strain AYE. Interestingly, the latter has even higher catabolic capacities than A. baylyi which has already been reported as a very nutritionally versatile organism. This metabolic performance could explain the persistence of A. baumannii nosocomial strains in environments where nutrients are scarce; iii) several processes known to play a key role during host infection (biofilm formation, iron uptake, quorum sensing, virulence factors) were either different or absent, the best example of which is iron uptake. Indeed, strain AYE and A. baylyi use siderophore-based systems to scavenge iron from the environment whereas strain SDF uses an alternate system similar to the Haem Acquisition System (HAS). Taken together, all these observations suggest that the genome contents of the 3 Acinetobacters compared are partly shaped by life in distinct ecological niches: human (and more largely hospital environment), louse, soil

The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner

Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of adult C57BL6 wild-type mice treated with a single systemic dose of MAM acetate display DNA damage (O6-methyldeoxyguanosine lesions, O6-mG) that remains constant up to 7 days post-treatment. By contrast, MAM-treated mice lacking a functional gene encoding the DNA repair enzyme O6-mG DNA methyltransferase (MGMT) showed elevated O6-mG DNA damage starting at 48 hours post-treatment. The DNA damage was linked to changes in the expression of genes in cell-signaling pathways associated with cancer, human neurodegenerative disease, and neurodevelopmental disorders. These data are consistent with the established developmental neurotoxic and carcinogenic properties of MAM in rodents. They also support the hypothesis that early-life exposure to MAM-glucoside (cycasin) has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for food or medicine, or both. These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer) or not (neurodegeneration). Exposure to MAM-related environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer's disease