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OBJECTIVE: This study investigated the onset and the choice of treatment in children with very early onset of type 1 diabetes mellitus (T1D). METHODS: The study included 5,763 patients from the German Diabetes Patient Follow-up registry with onset of T1D in the first 4 years of life from January 2010 - June 2022. The analysis included diabetes-specific parameters, anthropometric data, and mode of treatment at onset, within the first and second year of T1D. Three groups were compared according to age at onset (G1: 223 patients 6-<12 months, G2: 1519 patients 12-<24 months, G3: 4001 patients 24-48 months). RESULTS: In 12.3% of all cases in childhood and adolescence, the incidence of diabetes in the first 4 years of life was rare. At the onset, clinical status was worse and diabetic ketoacidosis (DKA) rates were higher in G1 and G2 (52.3% and 46.5%, respectively) compared to G3 (27.3% (p<0.001)). G1 and G2 were significantly more likely to be treated with insulin pump therapy (CSII) 2 years after onset (98.1% and 94.1%, respectively)) compared to G3 (85.8%, p<0.001). Median HbA1c after 2 years did not differ between groups (G1: 7.27% (56.0 mmol/mol), G2: 7.34% (56.7 mmol/mol) and G3: 7.27% (56.0 mmol/mol)) or when comparing CSII vs MDI. The rate of severe hypoglycemia (SH) and DKA during the first 2 years of treatment did not differ among the three groups, ranging from 1.83-2.63/100 patient-years (PY) for DKA and 9.37-24.2/100 PY for SH. Children with T1D under 4 years of age are more likely to be diagnosed with celiac disease but less likely to have thyroiditis than older children with T1DM. CONCLUSIONS: Young children with T1D had high rates of DKA at onset and were predominantly treated with insulin pump therapy during the first 2 years. The median HbA1c for all three groups was<7.5% (58 mmol/mol) without increased risk of SH or DKA. The use of continuous glucose monitoring (CGM) was not associated with lower HbA1c in children under 48 months.
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Edad de Inicio , Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/sangre , Lactante , Preescolar , Masculino , Femenino , Alemania/epidemiología , Adolescente , Progresión de la Enfermedad , Sistema de Registros , Sistemas de Infusión de Insulina , Hipoglucemiantes/administración & dosificación , Niño , Insulina/administración & dosificación , Cetoacidosis Diabética/epidemiología , Cetoacidosis Diabética/terapiaRESUMEN
OBJECTIVES: To study the potential association between increases in daily mean air temperature and time below range (TBR <54 mg/dl) and time above range (TAR >250 mg/dl) in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Individuals with type 1 diabetes <21 years with information on daily glucose profiles from the diabetes prospective follow-up study (DPV) were included (n = 2582). Further inclusion criteria were age at least 6 months at diabetes onset, diabetes duration for at least one year and treatment years 2020-2021. Mean daily air temperature and other meteorological parameters from 78 measurement stations in Germany were linked to the individual glucose sensor profile via the five-digit postcode areas of residency. We used multivariable repeated measures fractional logistic regression models with a compound symmetry covariance structure to study the association between a 1 °C increase in daily mean temperature and time in specific glucose ranges. RESULTS: A 1 °C increase in daily mean temperature was associated with an acute (Odds Ratio (OR) 1.009 (95%-CI 1.007, 1.011)) and up to 7 days delayed (OR 1.003 (1.001, 1.005)) increase in TBR <54 mg/dl. Moreover, an acute decrease in TAR >250 mg/dl (OR 0.997 (0.996, 0.997)) was found. CONCLUSIONS: Results of the DPV registry showed small, but statistically significant changes in TBR and TAR in association with a short-term temperature increase. Higher blood flow and faster insulin absorption might be one possible mechanism. In times of increasing temperature fluctuations meteorological impacts on time in range could become even more relevant.
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Diabetes Mellitus Tipo 1 , Hipoglucemia , Humanos , Niño , Adolescente , Diabetes Mellitus Tipo 1/epidemiología , Temperatura , Estudios Prospectivos , Estudios de Seguimiento , Hipoglucemia/epidemiología , Hipoglucemia/etiología , Insulina , Glucosa , GlucemiaRESUMEN
van der Waals crystals have opened a new and exciting chapter in heterostructure research, removing the lattice matching constraint characteristics of epitaxial semiconductors. They provide unprecedented flexibility for heterostructure design. Combining two-dimensional (2D) perovskites with other 2D materials, in particular transition metal dichalcogenides (TMDs), has recently emerged as an intriguing way to design hybrid opto-electronic devices. However, the excitation transfer mechanism between the layers (charge or energy transfer) remains to be elucidated. Here, we investigate PEA2PbI4/MoSe2 and (BA)2PbI4/MoSe2 heterostructures by combining optical spectroscopy and density functional theory (DFT) calculations. We show that band alignment facilitates charge transfer. Namely, holes are transferred from TMDs to 2D perovskites, while the electron transfer is blocked, resulting in the formation of interlayer excitons. Moreover, we show that the energy transfer mechanism can be turned on by an appropriate alignment of the excitonic states, providing a rule of thumb for the deterministic control of the excitation transfer mechanism in TMD/2D-perovskite heterostructures.
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We report on the observation of terahertz (THz) radiation induced band-to-band impact ionization in HgTe quantum well (QW) structures of critical thickness, which are characterized by a nearly linear energy dispersion. The THz electric field drives the carriers initializing electron-hole pair generation. The carrier multiplication is observed for photon energies less than the energy gap under the condition that the product of the radiation angular frequency ω and momentum relaxation time τ l larger than unity. In this case, the charge carriers acquire high energies solely because of collisions in the presence of a high-frequency electric field. The developed microscopic theory shows that the probability of the light-induced impact ionization is proportional to exp ( - E 0 2 / E 2 ) , with the radiation electric field amplitude E and the characteristic field parameter E 0. As observed in experiment, it exhibits a strong frequency dependence for ω τ â« 1 characterized by the characteristic field E 0 linearly increasing with the radiation frequency ω.
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We used Gaussian separation and receiver operating characteristic (ROC) curves to optimize the neutron sensitivity and gamma rejection of an ultra-thin 6LiF:ZnS(Ag)-scintillator-based neutron detector paired with a silicon photomultiplier (SiPM). We recorded the waveforms while operating the detector in a monochromatic cold neutron beam and in the presence of isotopic 137Cs and 60Co gamma sources. We used a two-window charge comparison (CC) pulse-shape discrimination (PSD) technique to distinguish the neutron capture events from other types of signals. By feeding the recorded waveforms through variants of this algorithm, it was possible to optimize the duration of the integration windows [(0-100 ns) for the prompt window and (100-2300 ns)] for the delayed window. We then computed the detector's ROC curve from waveform recordings and compared that with the experimental performance. We also used this procedure to compare a series of detector configurations to select the optimal bias voltage for the SiPM photosensor.
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Amino acids (AAs), important constituents of natural moisturizing factors (NMFs) of the skin are decreased in diseased conditions such as psoriasis and atopic dermatitis. No study so far investigated the uptake of AAs into isolated corneocytes (COR). The present study was performed using 19 AAs, including taurine (TAU), to measure their amount diffused into the COR and binding of these AAs to keratin. Incubation of alanine, aspartic acid, asparagine, glutamine, glutamic acid, histidine, proline, serine and TAU with the isolated COR showed uptake after 24 h of 51.6, 95.4, 98.6, 94.1, 95.6, 90.1, 94.6, 72.9 and 57.8 %, respectively, into the COR but no binding with keratin. Uptake of TAU was validated by time dependent in-vitro diffusion models 'without COR and 'with COR'. The time dependent curve fitting showed that in in-vitro diffusion model 'without COR' there was no change in the total concentration of TAU until 72 hours, while in diffusion model 'with COR' the total conc. decreased to 37.8 % after 72 hours. The Pearson's correlation coefficient 'r' between the conc. curves of both in-vitro diffusion models was -0.54 that was an evidence of significant amount of TAU uptake by the COR. AAs as part of the NMFs have a great potential to be diffused into the COR. This property of the AAs can be employed in further dermatological research on diseased or aged skin conditions with NMFs deficiency.
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Aminoácidos/metabolismo , Difusión , Epidermis/metabolismo , Taurina/metabolismoRESUMEN
BACKGROUND: Intestinal absorption of hypoglycin A (HGA) and its metabolism are considered major prerequisites for atypical myopathy (AM). The increasing incidence and the high mortality rate of AM urgently necessitate new therapeutic and/or preventative approaches. OBJECTIVES: To identify a substance for oral administration capable of binding HGA in the intestinal lumen and effectively reducing the intestinal absorption of the toxin. STUDY DESIGN: Experimental in vitro study. METHODS: Substances commonly used in equine practice (activated charcoal composition, di-tri-octahedral smectite, mineral oil and activated charcoal) were tested for their binding capacity for HGA using an in vitro incubation method. The substance most effective in binding HGA was subsequently tested for its potential to reduce intestinal HGA absorption. Jejunal tissues of 6 horses were incubated in Ussing chambers to determine mucosal uptake, tissue accumulation, and serosal release of HGA in the presence and absence of the target substance. Potential intestinal metabolism in methylenecyclopropyl acetic acid (MCPA)-conjugates was investigated by analysing their concentrations in samples from the Ussing chambers. RESULTS: Activated charcoal composition and activated charcoal were identified as potent HGA binding substances with dose and pH dependent binding capacity. There was no evidence of intestinal HGA metabolism. MAIN LIMITATIONS: Binding capacity of adsorbents was tested in vitro using aqueous solutions, and in vivo factors such as transit time and composition of intestinal content, may affect adsorption capacity after oral administration. CONCLUSIONS: For the first time, this study identifies substances capable of reducing HGA intestinal absorption. This might have major implications as a preventive measure in cograzers of AM affected horses but also in horses at an early stage of intoxication.
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Acer/química , Antídotos/farmacología , Enfermedades de los Caballos/inducido químicamente , Hipoglicinas/toxicidad , Rabdomiólisis/veterinaria , Adsorción , Animales , Antídotos/química , Carbón Orgánico/administración & dosificación , Carbón Orgánico/química , Carbón Orgánico/farmacología , Combinación de Medicamentos , Enfermedades de los Caballos/prevención & control , Caballos , Hipoglicinas/química , Caolín , Corteza de la Planta/química , Intoxicación por Plantas/veterinaria , Quercus/química , Rabdomiólisis/inducido químicamente , Semillas/química , Silicatos/administración & dosificación , Silicatos/química , Silicatos/farmacología , Dióxido de Silicio/administración & dosificación , Dióxido de Silicio/química , Dióxido de Silicio/farmacologíaRESUMEN
Objective of this study was to analyze prevalence changes in type 2 diabetes (T2D) among children and adolescents over the last 10 years. We performed a cross-sectional survey in Baden-Württemberg (BW), Germany, by using a written questionnaire and comparing these results with T2D prevalence data from the same area retrieved in 2004/2005. In 2016, 50 patients with T2D under 20 years of age were registered in BW, Germany, which corresponds to a prevalence rate of 2.42 per 100 000 (95% confidence interval [CI]: 1.75-3.09). The prevalence rate found in the same geographic area 10 years prior was 2.30 per 100 000 (95% CI: 1.70-2.90). Overall, 70% of T2D patients of this age group were treated by adult diabetologists. Concisely the prevalence of T2D in children and adolescents is still low in South Germany, remaining practically unchanged over the past decade.
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Diabetes Mellitus Tipo 2/epidemiología , Adolescente , Adulto , Niño , Preescolar , Estudios Transversales , Femenino , Alemania/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Prevalencia , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Hamburg is a growing metropolitan city. The increase in sealed surfaces of about 0.36% per year and the subsequent increased runoff impacts on the city's wastewater infrastructure. Further potential risks to the drainage infrastructure arise also from effects of climate change, e.g. increased intensity and frequency of heavy rainfalls. These challenges were addressed in the Rain InfraStructure Adaption (RISA) project conducted 2009-2015 by HAMBURG WASSER and the State Ministry for Environment and Energy, supported by several municipal stakeholders. RISA addressed intensifying conflicts in the context of urban development and stormwater management at that time. Major results of the project are improvements and recommendations for adequate consideration of stormwater management issues during urban planning as well as new funding mechanisms for stormwater management measures. The latter topic resulted in the introduction of a separated stormwater charge based on the amount of sealed area connected to the sewer system of each property. For both undertakings - the RISA project and the introduction of the separated stormwater charge - a novel, comprehensive, digital database was built. Today, these geographical information system (GIS)-based data offer various scale-independent analysis and information opportunities, which facilitate the day-to-day business of HAMBURG WASSER and stormwater management practice in Hamburg.
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Ciudades , Planificación de Ciudades , Ingeniería Sanitaria/economía , Ingeniería Sanitaria/métodos , Movimientos del Agua , Cambio Climático , Ambiente , Monitoreo del Ambiente , Sistemas de Información Geográfica , Alemania , Lluvia , Eliminación de Residuos Líquidos/métodosRESUMEN
We measure the quantum capacitance and probe thus directly the electronic density of states of the high mobility, Dirac type two-dimensional electron system, which forms on the surface of strained HgTe. Here we show that observed magnetocapacitance oscillations probe-in contrast to magnetotransport-primarily the top surface. Capacitance measurements constitute thus a powerful tool to probe only one topological surface and to reconstruct its Landau level spectrum for different positions of the Fermi energy.
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BACKGROUND: Prevention guidelines for infants at high risk of allergic disease recommend hydrolysed formula if formula is introduced before 6 months, but evidence is mixed. Adding specific oligosaccharides may improve outcomes. OBJECTIVE: To evaluate whether partially hydrolysed whey formula containing oligosaccharides (0.8 g/100 ml) (pHF-OS) can prevent eczema in high-risk infants [ISRCTN65195597]. METHODS: We conducted a parallel-group, multicentre, randomized double-blind controlled trial of pHF-OS vs standard cow's milk formula. Infants with a family history of allergic disease were randomized (stratified by centre/maternal allergy) to active (n = 432) or control (n = 431) formula until 6 months of age if formula was introduced before 18 weeks. Primary outcome was cumulative incidence of eczema by 12 months in infants randomized at 0-4 weeks (375 pHF-OS, 383 control). Secondary outcomes were cumulative incidence of eczema by 12 or 18 months in all infants randomized, immune markers at 6 months and adverse events. RESULTS: Eczema occurred by 12 months in 84/293 (28.7%) infants allocated to pHF-OS at 0-4 weeks of age, vs 93/324 (28.7%) control (OR 0.98 95% CI 0.68, 1.40; P = 0.90), and 107/347 (30.8%) pHF-OS vs 112/370 (30.3%) control in all infants randomized (OR 0.99 95% CI 0.71, 1.37; P = 0.94). pHF-OS did not change most immune markers including total/specific IgE; however, pHF-OS reduced cow's milk-specific IgG1 (P < 0.0001) and increased regulatory T-cell and plasmacytoid dendritic cell percentages. There was no group difference in adverse events. CONCLUSION: pHF-OS does not prevent eczema in the first year in high-risk infants. The immunological changes found require confirmation in a separate cohort.
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Suplementos Dietéticos , Eccema/prevención & control , Fórmulas Infantiles , Leche/inmunología , Prebióticos/administración & dosificación , Adulto , Alérgenos/inmunología , Animales , Biomarcadores , Bovinos , Citocinas , Eccema/epidemiología , Eccema/etiología , Femenino , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Incidencia , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Masculino , Hipersensibilidad a la Leche/epidemiología , Hipersensibilidad a la Leche/prevención & control , Factores de RiesgoRESUMEN
OBJECTIVES: We evaluated the pharmacokinetics, safety and tolerability of two different continuous treatment regimens of tobramycin inhalation solution (TIS) in 29 cystic fibrosis (CF) patients chronically infected with Pseudomonas aeruginosa. PATIENTS AND METHODS: In this randomized, multicentre, open-label, two-period crossover study, TIS (300 mg/5 mL) was administered via PARI eFlow(®) rapid once daily and twice daily each for 8 weeks. Serum pharmacokinetics of these two regimens was analysed. Tobramycin levels were determined before the morning dose and at 30, 60 and 90 min after the end of nebulization in the middle and at the end of each 8 week cycle. At these timepoints, trough and peak serum tobramycin concentrations (Cmax, mg/L) as well as the area under the curve for 0-90 min of tobramycin (AUC0-90min) were assessed in order to evaluate the risk of systemic toxicity. Safety parameters and forced expiratory volume in 1 s (FEV1) were assessed. RESULTS: For once-daily treatment, tobramycin levels were 10% higher after 8 weeks compared with 4 weeks (AUC0-90min ratioâ=â1.096, 90% CIâ=â0.860-1.396, Pâ=â0.5237). For twice-daily treatment, tobramycin levels after 8 weeks showed a 40% decrease compared with 4 weeks (AUC0-90min ratioâ=â0.608, 90% CIâ=â0.461-0.802, Pâ=â0.0055). The AUC0-90min ratio at 8 weeks (once daily versus twice daily) did not differ significantly (AUC0-90min ratioâ=â0.749, 90% CIâ=â0.514-1.092, Pâ=â0.2009). The mean FEV1 did not differ markedly compared between treatment periods or with baseline. No audiological or nephrotoxic side effects were noted. CONCLUSIONS: Continuous treatment with TIS (once daily or twice daily) over 8 weeks appears to be safe and tolerable.
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Antibacterianos/administración & dosificación , Fibrosis Quística/complicaciones , Neumonía Bacteriana/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Tobramicina/administración & dosificación , Administración por Inhalación , Adolescente , Adulto , Antibacterianos/efectos adversos , Antibacterianos/farmacocinética , Niño , Estudios Cruzados , Femenino , Humanos , Masculino , Pseudomonas aeruginosa/efectos de los fármacos , Suero/química , Tobramicina/efectos adversos , Tobramicina/farmacocinética , Adulto JovenRESUMEN
Willow bark extracts are used for the treatment of fever, pain and inflammation. Recent clinical and pharmacological research revealed that not only the salicylic alcohol derivatives, but also the polyphenols significantly contribute to these effects. Quantitative analysis of the European Pharmacopoeia still focuses on the determination of the salicylic alcohol derivatives. The objective of the present study was the development of an effective quantification method for the determination of as many flavanone and chalcone glycosides as possible in Salix purpurea and other Salix species as well as commercial preparations thereof. As Salix species contain a diverse spectrum of the glycosidated flavanones naringenin, eriodictyol, and the chalcone chalconaringenin, a subsequent acidic and enzymatic hydrolysis was developed to yield naringenin and eriodictyol as aglycones, which were quantified by HPLC. The 5-O-glucosides were cleaved with 11.5% TFA before subsequent hydrolysis of the 7-O-glucosides with an almond ß-glucosidase at pH 6-7. The method was validated with regard to LOD, LOQ, intraday and interday precision, accuracy, stability, recovery, time of hydrolysis, robustness and applicability to extracts. All 5-O- and 7-O-glucosides of naringenin, eriodictyol and chalconaringenin were completely hydrolysed and converted to naringenin and eriodictyol. The LOD of the HPLC method was 0.77 µM of naringenin and 0.45 µM of eriodictyol. The LOQ was 2.34 µM of naringenin and 1.35 µM for eriodictyol. The method is robust with regard to sample weight, but susceptible concerning enzyme deterioration. The developed method is applicable to the determination of flavanone and chalcone glycosides in willow bark and corresponding preparations.
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Chalconas/análisis , Flavonas/análisis , Corteza de la Planta/química , Salix/química , Cromatografía Líquida de Alta Presión , Indicadores y Reactivos , Límite de Detección , Estándares de Referencia , Reproducibilidad de los ResultadosRESUMEN
A commercially available assay (eazyplex® SuperBug CRE) detecting the most common carbapenemase and ESBL types was evaluated directly on 50 urine samples. Eazyplex® correctly detected ESBL-encoding genes in all 30 urine samples with confirmed ESBL production (sensitivity 100%). Two specimens showed invalid and one specimen false-positive results (specificity 97.9%).
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Proteínas Bacterianas/orina , Infecciones por Enterobacteriaceae/orina , Enterobacteriaceae/enzimología , Técnicas de Amplificación de Ácido Nucleico/métodos , beta-Lactamasas/orina , Proteínas Bacterianas/genética , Enterobacteriaceae/genética , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Humanos , Técnicas de Amplificación de Ácido Nucleico/economía , Juego de Reactivos para Diagnóstico , beta-Lactamasas/genéticaRESUMEN
Hypoglycin A (HGA) in seeds of Acer spp. is suspected to cause seasonal pasture myopathy in North America and equine atypical myopathy (AM) in Europe, fatal diseases in horses on pasture. In previous studies, this suspicion was substantiated by the correlation of seed HGA content with the concentrations of toxic metabolites in urine and serum (MCPA-conjugates) of affected horses. However, seed sampling was conducted after rather than during an outbreak of the disease. The aim of this study was to further confirm the causality between HGA occurrence and disease outbreak by seed sampling during an outbreak and the determination of i) HGA in seeds and of ii) HGA and MCPA-conjugates in urine and serum of diseased horses. Furthermore, cograzing healthy horses, which were present on AM affected pastures, were also investigated. AM-pastures in Germany were visited to identify seeds of Acer pseudoplatanus and serum (n = 8) as well as urine (n = 6) from a total of 16 diseased horses were analyzed for amino acid composition by LC-ESI-MS/MS, with a special focus on the content of HGA. Additionally, the content of its toxic metabolite was measured in its conjugated form in body fluids (UPLC-MS/MS). The seeds contained 1.7-319.8 µg HGA/g seed. The content of HGA in serum of affected horses ranged from 387.8-8493.8 µg/L (controls < 10 µg/L), and in urine from 143.8-926.4 µg/L (controls < 10 µg/L), respectively. Healthy cograzing horses on AM-pastures showed higher serum (108.8 ± 83.76 µg/L) and urine concentrations (26.9 ± 7.39 µg/L) compared to control horses, but lower concentrations compared to diseased horses. The range of MCPA-carnitine and creatinine concentrations found in diseased horses in serum and urine were 0.17-0.65 mmol/L (controls < 0.01), and 0.34-2.05 µmol/mmoL (controls < 0.001), respectively. MCPA-glycine levels in urine of cograzing horses were higher compared to controls. Thus, the causal link between HGA intoxication and disease outbreak could be further substantiated, and the early detection of HGA in cograzing horses, which are clinically normal, might be a promising step in prophylaxis.
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Enfermedades de los Caballos/diagnóstico , Hipoglicinas/sangre , Hipoglicinas/orina , Enfermedades Musculares/veterinaria , Intoxicación por Plantas/veterinaria , Acer/envenenamiento , Animales , Carnitina/análogos & derivados , Carnitina/sangre , Carnitina/orina , Brotes de Enfermedades , Enfermedades de los Caballos/sangre , Enfermedades de los Caballos/orina , Caballos , Hipoglicinas/envenenamiento , Enfermedades Musculares/sangre , Enfermedades Musculares/inducido químicamente , Intoxicación por Plantas/sangre , Intoxicación por Plantas/orina , Plantas Tóxicas/envenenamiento , Semillas/química , Semillas/envenenamiento , Espectrometría de Masas en TándemRESUMEN
Plastic mulching (PM) is widely used in modern agriculture because of its advantageous effects on soil temperature and water conservation, factors which strongly influence the microbiology of the soil. The aim of this study was to assess the effect of PM on mycotoxin occurrence in relation with mycobiome abundance/diversity and soil physicochemical properties. Soil samples were collected from green (GA) and white asparagus (WA) crops, the last under PM. Both crops were cultivated in a ridge-furrow-ridge system without irrigation. Samples were analyzed for mycotoxin occurrence via liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Total colony-forming unit was indicative of mycobiome abundance, and analysis of mycobiome diversity was performed by internal transcribed spacer (ITS) sequencing. PM avoided the drop of soil temperature in winter and allowed higher soil temperature in early spring compared to non-covered soil. Moreover, the use of PM provided controlled conditions for water content in soil. This was enough to generate a dissimilar mycotoxin occurrence and mycobiome diversity/abundance in covered and non-covered soil. Mycotoxin soil contamination was confirmed for deoxynivalenol (DON), range LOD to 32.1 ng/g (LOD = 1.1 ng/g). The DON values were higher under PM (average 16.9 ± 10.1 ng/g) than in non-covered soil (9.1 ± 7.9 ng/g); however, this difference was not statically significant (p = 0.09). Mycobiome analysis showed a fungal compartment up to fivefold higher in soil under PM compared to GA. The diversity of the mycobiome varied between crops and also along the soil column, with an important dominance of Fusarium species at the root zone in covered soils.
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Agricultura/métodos , Biodiversidad , Hongos/aislamiento & purificación , Liliaceae/crecimiento & desarrollo , Micotoxinas/análisis , Microbiología del Suelo , Suelo/química , Cromatografía Liquida , Análisis por Conglomerados , ADN de Hongos/química , ADN de Hongos/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Hongos/clasificación , Espectrometría de Masas , Datos de Secuencia Molecular , Filogenia , Plásticos , Análisis de Secuencia de ADNRESUMEN
A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.
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Complejo CD3/genética , Lupus Eritematoso Sistémico/etnología , Lupus Eritematoso Sistémico/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Linfocitos T/inmunología , Población Blanca/genéticaRESUMEN
OBJECTIVES: The objectives of this paper are to prospectively determine the incidence of paediatric systemic lupus erythematosus (pSLE) in Australia as well as describe the demographics, clinical presentation and one-year outcome. STUDY DESIGN: Newly diagnosed cases of pSLE were ascertained prospectively from October 2009 to October 2011 through the Australian Paediatric Surveillance Unit (a national monthly surveillance scheme for notification of childhood rare diseases) as well as national subspecialty groups. Questionnaires were sent to notifying physicians at presentation and at one year. RESULTS: The annual incidence rate was 0.32 per 10(5) children aged less than 16 years. The incidence was significantly higher in children of Asian or Australian Aboriginal and Torres Strait Islander parents. Approximately one-third of children underwent a renal biopsy at presentation and 7% required dialysis initially although only one child had end-stage kidney disease (ESKD) at one-year follow-up. CONCLUSION: The incidence of pSLE in Australia is comparable to that worldwide with a significantly higher incidence seen in children of Asian and Australian Aboriginal and Torres Strait Islander backgrounds. Renal involvement is common but progression to ESKD, at least in the short term, is rare.
Asunto(s)
Pueblo Asiatico/estadística & datos numéricos , Lupus Eritematoso Sistémico/epidemiología , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Adolescente , Edad de Inicio , Anticuerpos Antinucleares/sangre , Australia/epidemiología , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/etnología , Nefritis Lúpica/epidemiología , Nefritis Lúpica/patología , Nefritis Lúpica/terapia , Masculino , Estudios Prospectivos , Proteinuria/etiología , Fiebre Reumática/etiologíaRESUMEN
X-linked severe combined immunodeficiency is caused by mutations in the IL-2 receptor common gamma chain and classically presents in the first 6 months of life with predisposition to bacterial, viral and fungal infections. In most instances, affected individuals are lymphopenic with near complete absence of T cells and NK cells. We report a boy who presented at 12 months of age with Pneumocystis jiroveci pneumonia and a family history consistent with X-linked recessive inheritance. He had a normal lymphocyte count including the presence of T cells and a broad T-cell-receptor diversity, as well as normal surface expression of the common gamma chain (CD132) protein. He however had profound hypogammaglobulinaemia, and IL-2-induced STAT5 phosphorylation was absent. Sequencing of IL-2RG demonstrated a 12-base pair intronic deletion close to the canonical splice site of exon 5, which resulted in a variety of truncated IL2RG mRNA species. A review of the literature identified 4 other patients with T-cell-positive X-SCID, with the current patient being the first associated with an mRNA splicing defect. This case raises the question of how a dysfunctional protein incapable of mediating STAT5 phosphorylation might nonetheless support T-cell development. Possible explanations are that STAT5-mediated signal transduction may be less relevant to IL7-receptor-mediated T-cell development than are other IL7R-induced intracellular transduction pathways or that a low level of STAT5 phosphorylation, undetectable in the laboratory, may be sufficient to support some T-cell development.
Asunto(s)
Agammaglobulinemia/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Subunidad gamma Común de Receptores de Interleucina/genética , Neumonía por Pneumocystis/inmunología , Eliminación de Secuencia/genética , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/genética , Humanos , Lactante , Recuento de Linfocitos , Masculino , Fosforilación/genética , Pneumocystis carinii/inmunología , Pneumocystis carinii/patogenicidad , Neumonía por Pneumocystis/microbiología , ARN Mensajero/genética , Factor de Transcripción STAT5/metabolismo , Linfocitos T/inmunología , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/inmunologíaRESUMEN
OBJECTIVE: To evaluate the efficacy of inducing labour using a double-balloon catheter and oral misoprostol sequentially, in comparison with oral misoprostol alone. DESIGN: A multicentre randomised controlled trial. SETTING: Five hospitals in Germany. POPULATION: A total of 326 pregnant women with an unfavourable cervix undergoing labour induction at term. METHODS: Women were randomly assigned according to a computer-generated allocation sequence to sequential use of double-balloon catheter and oral misoprostol (study group) or oral misoprostol alone (control group). In the study group, the double-balloon catheter was used the first day before starting oral misoprostol the second day. MAIN OUTCOME MEASURES: The primary outcome measure was the induction-to-delivery interval, and a further outcome parameter was delivery within 48 hours. RESULTS: The median times for induction of labour until delivery were 32.4 hours in the study group and 22.5 hours in the control group (P = 0.004). This difference was not seen when evaluating according to parity (nulliparous, P = 0.19; parous, P = 0.06). The rate of vaginal delivery within 48 hours did not differ between both groups. The number of applications of misoprostol (two versus three, P < 0.001) and the dose of misoprostol used was lower in the study group (100 versus 200 µg, P < 0.001). In the study group, there were more Apgar scores of <7 at 5 minutes (8 versus 1, P = 0.04). CONCLUSIONS: The use of a double-balloon catheter on the first day, before starting oral misoprostol on the second day, did not improve the induction to delivery interval and the rate of delivery within 48 hours, in comparison with oral misoprostol alone.