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INTRODUCTION: There is growing interest in the prediagnostic phase of inflammatory bowel disease (IBD) and in the overlap of IBD with other diseases. We described and compared use of any prescription medication between individuals with and without IBD in a 10-year period preceding diagnosis. METHODS: Based on cross-linked nationwide registers, we identified 29,219 individuals diagnosed with IBD in Denmark between 2005 and 2018 and matched to 292,190 IBD-free individuals. The primary outcome was use of any prescription medication in years 1-10 before IBD diagnosis/matching date. Participants were considered as medication users if they redeemed ≥1 prescription for any medication in the World Health Organization Anatomical Therapeutic Chemical (ATC) main groups or subgroups before diagnosis/matching. RESULTS: The IBD population had a universally increased use of medications compared with the matched population before IBD diagnosis. At 10 years before diagnosis, the proportion of users was 1.1-fold to 1.8-fold higher in the IBD population in 12 of 14 ATC main groups of medication ( P -value < 0.0001). This applied across age, sex, and IBD subtypes, although it was the most pronounced for Crohn's disease (CD). Two years before diagnosis, the IBD population had a steep increase in medication use for several organ systems. When analyzing therapeutic subgroups of medication, the CD population exhibited 2.7, 2.3, 1.9, and 1.9 times more users of immunosuppressants, antianemic preparations, analgesics, and psycholeptics, respectively, than the matched population 10 years before diagnosis ( P -value < 0.0001). DISCUSSION: Our findings demonstrate universally increased medication use years before IBD, especially CD, diagnosis and indicates multiorgan involvement in IBD.
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Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Medicamentos bajo Prescripción , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/epidemiología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/epidemiología , Analgésicos/uso terapéutico , Inmunosupresores/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológicoRESUMEN
In order to establish design criteria for Rh C-H borylation catalysts, analogues of the successful catalyst [Rh(Ind)(SIDipp)(COE)] (Ind = η5-indenyl, SIDipp = 1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene, and COE = cis-cyclooctene) were synthesized by changing the indenyl and carbene ligands. [RhCp(SIDipp)(COE)] (1) formed alongside the C-C activated, cyclometalated byproduct [RhCp(κ2CAr,Ccarbene-SIDipp')(iPr)] (rac-2; SIDipp' = 1-(6-isopropylphenyl)-3-(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene). Computational modeling of COE dissociation showed that both C-C and C-H activation of the SIDipp aryl group is thermally attainable and reversible under experimental conditions, with the C-C activation products being the more thermodynamically stable species. Oxidative addition of 1 with SiH(OEt)3 gave the Rh silyl hydride [RhCp(H){Si(OEt)3}(SIDipp)] (rac-3). [Rh(Ind)(IDipp)(COE)] (4; IDipp = 1,3-bis(2,6-diisopropylphenyl)-imidazole-2-ylidene), the carbonyl analogue [Rh(Ind)(IDipp)(CO)] (5; νCO = 1940 cm-1, cf. 1944 cm-1 for [Rh(Ind)(SIDipp)(COE)]), and [Rh(Ind)(IMe4)(COE)] (6; IMe4 = 1,3,4,5-tetramethylimidazol-2-ylidene) were also characterized, but attempts to synthesize Rh carbene complexes with fluorenyl or 1,2,3,4-tetrahydrofluorenyl ligands were not successful. For the catalytic C-H borylation of benzene using B2pin2, 1 was inactive at 80 °C, and [Rh(Ind)(SIDipp)(COE)] was superior to all other complexes tested due to the shortest induction period. However, the addition of HBpin to precatalyst 4 eliminated the induction period. Catalytic n-alkane C-H borylation using [Rh(Ind)(NHC)(COE)] gave yields of up to 21% alkylBpin, but [RhCp*(C2H4)2] was the better catalyst.
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Advanced analytical techniques have identified the heterogeneity of sediments in aquatic environments which may impact the exposure of benthic organisms to contaminants. Acute and chronic toxicity associated with short, intermittent exposure to four field-collected contaminated sediments were assessed for the epi-benthic amphipod Melita plumulosa and the harpacticoid copepod Nitocra spinipes. Increasing the duration of exposure caused a decrease in survival of M. plumulosa and N. spinipes during 10-d bioassays. Increasing the frequency of exposure to a total exposure time >96-h resulted in a significant toxicity to M. plumulosa. Reproduction decreased for both species from exposure to contaminated sediment. For M. plumulosa, reproductive effects occurred for shorter exposures than the time taken to sense and avoid contaminant exposure. Thus, while avoidance behaviors may prevent acute lethality, slow responses may not prevent sublethal effects. Exposure of M. plumulosa to contaminated sediment appeared to cause a physiological change in females which reduced fecundity. This study indicates that sediment toxicity methods which utilize static continuous exposures may overestimate the toxicity that would occur at a field location. However, by preventing organisms from avoiding unfavorable sediments, these methods provide a precautionary assessment of possible effects, which is usually the aim of most assessments frameworks.
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Sedimentos Geológicos , Invertebrados/efectos de los fármacos , Pruebas de Toxicidad/métodos , Contaminantes Químicos del Agua/toxicidad , Anfípodos/efectos de los fármacos , Anfípodos/fisiología , Animales , Organismos Acuáticos/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Femenino , Fertilidad , Masculino , Reproducción , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad CrónicaRESUMEN
The relatively short life cycles of harpacticoid copepods makes them appropriate animals for use in tests that rapidly assess the acute, sublethal, or chronic effects of sediment contaminants. In this study, four harpacticoid copepod species (Nitocra spinipes, Tisbe tenuimana, Robertgurneya hopkinsi, and Halectinosoma sp.) were isolated from clean marine sediments, and procedures for laboratory culturing were developed. Halectinosoma sp. was abandoned due to handling difficulties. For the remaining species, the influence of food type and quantity on life-cycle progression was assessed. A mixed diet, comprising two species of algae (Tetraselmis sp. and Isochrysis sp.) and fish food (Sera Micron) was found to maintain healthy cultures and was fed during laboratory tests. Water-only exposure to dissolved copper (Cu) showed that the times (range) required to cause 50% lethality (LT(50)) were 24 (22-27) h at 50 µg Cu/l for T. tenuimana; 114 (100-131) and 36 (32-40) h for 200 and 400 µg Cu/l, respectively, for N. spinipes; and 119 (71-201) and 25 (18-33) h for 200 and 400 µg Cu/l, respectively, for R. hopkinsi. 96-h LC(50) (concentration causing 50% lethality) were also determined for adult N. spinipes exposed to cadmium, copper, zinc, ammonia, and phenol. A ranking system was generated based on the ease handling and culturing, rate of maturity, food selectivity and sensitivity to Cu. From this ranking, N. spinipes was determined to be the most suitable species for use in developing sediment-toxicity tests. The measurement of total reproductive output of N. spinipes during 10-day exposure to whole sediment was found to provide a useful end point for assessing the effects of sediment contamination.
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Copépodos/efectos de los fármacos , Ecotoxicología/métodos , Monitoreo del Ambiente/métodos , Sedimentos Geológicos/análisis , Amoníaco/toxicidad , Animales , Cadmio/toxicidad , Cobre/toxicidad , Estadios del Ciclo de Vida/efectos de los fármacos , Reproducción/efectos de los fármacos , Pruebas de Toxicidad/métodos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Zinc/toxicidadRESUMEN
We report a one-pot emulsion-templating strategy for the preparation of ZIF-8 microcapsules both in the presence and absence of surfactants. Capsule diameter is tuneable in the range 1-10 µm, and they can be post-synthetically etched with excess imidazole to form hierarchical architectures resembling Oleaceae pollen grains.
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The distribution of contaminants is seldom homogeneous in aquatic systems. In the present study, the avoidance response of Melita plumulosa, Nitocra spinipes, and Phallomedusa solida when exposed to contaminated sediments was investigated. Test vessels were designed to allow the congruent placement of two sediments and assessment of the movement of organisms between the sediments. When exposed to reference sediment, each species dispersed evenly between test chambers regardless of differences in sediment particle size. In the presence of contaminated sediment, the magnitude and rate of avoidance varied. Avoidance assays showed that test species avoided contaminated sediment as early as 6, 6, and 24 h following exposure for N. spinipes, P. solida, and M. plumulosa, respectively. The 48-h avoidance response of M. plumulosa for nine contaminated sediments of varying toxicity showed that avoidance was generally greater for sediments which elicited greater 10-d lethality to this species. The study demonstrated that each of these species has the ability to respond to chemical cues in the environment to inhabit sediment that provides the best opportunity for survival. The avoidance response for each species indicates the potential for developing rapid screening methods to assess sediment quality. Evidence suggests that avoidance was related to sediment toxicity and that static 10-d toxicity methods are likely to overestimate toxicity for species, which would avoid contamination in heterogeneous field settings.