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A new paradigm for energy is underway demanding decarbonized energy systems. Some of them rely on emerging electrochemical devices, crucial in hydrogen technologies, including fuel cells, CO2 and water electrolysers, whose applications and performances depend on key components such as their separators/ion-exchange membranes. The most studied and already commercialized Nafion membrane shows great chemical stability, but its water content limits its high proton conduction to a limited range of operating temperatures. Here, we report the synthesis of a new series of triazinephosphonate derivatives and their use as dopants in the preparation of new modified Nafion membranes. The triazinephosphonate derivatives were prepared by substitution of chlorine atoms in cyanuric chloride. Diverse conditions were used to obtain the trisubstituted (4-hydroxyphenyl)triazinephosphonate derivatives and the (4-aminophenyl)triazinephosphonate derivatives, but with these amino counterparts, only the disubstituted compounds were obtained. The new modified Nafion membranes were prepared by casting incorporation of the synthesized 1,3,5-triazinephosphonate (TPs) derivatives. The evaluation of the proton conduction properties of the new membranes and relative humidity (RH) conditions and at 60 °C, showed that they present higher proton conductivities than the prepared Nafion membrane and similar or better proton conductivities than commercial Nafion N115, in the same experimental conditions. The Nafion-doped membrane with compound TP2 with a 1.0 wt % loading showed the highest proton conductivity with 84 mS·cm-1.
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Using as functional form a combination of valence bond and mechanic molecular terms a new full-dimensional potential energy surface was developed for the title reaction, named PES-2022, which was fitted to high-level ab initio calculations at the coupled-cluster singles, doubles, and perturbative triples-F12 explicitly correlated level on a representative number of points describing the reactive system. This surface simultaneously describes the two reaction channels, hydrogen abstraction from the methyl group [(R1) path] and from the alcohol group [(R2) path] of methanol to form water. PES-2022 is a smooth and continuous surface, which reasonably describes the topology of this reactive system from reactants to products, including the intermediate complexes present in the system. Based on PES-2022 an exhaustive dynamics study was performed using quasi-classical trajectory calculations under two different initial conditions: at a fixed room temperature, for direct comparison with the experimental evidence and at different collision energies, to analyze possible mechanisms of reaction. In the first case, the available energy was mostly deposited as water vibrational energy, with the vibrational population inverted in the stretching modes and not inverted in the bending modes, reproducing the experimental evidence. In the second case, the analysis of different dynamics magnitudes (excitation functions, product energy partitioning, and product scattering distributions), allows us to suggest different mechanisms for both (R1) and (R2) paths: a direct mechanism for the (R2) path vs an indirect one, related with "nearly trapped" trajectories in the intermediate complexes, for the (R1) path.
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Purpose: The main purpose of this study was to report a case of cystoid macular edema (CME) after gonioscopy-assisted transluminal trabeculotomy (GATT). Methods: We describe the case of a 73-year-old woman with ocular hypertension and history of cataract surgery combined with posterior vitrectomy and epiretinal membrane peeling 2 years before, who developed CME after uncomplicated GATT procedure. Results: Uneventful GATT surgery was performed in an eye with ocular hypertension. A month after GATT surgery, the patient com-plained of blurry vision. Best corrected visual acuity had deteriorated from 20/20 on Snellen chart, to 20/70. The patient was diagnosed with CME. Treatment with topical non-steroidal anti-inflammatory drug (NSAID) and topical corticosteroids for one month, and oral carbonic anhydrase inhibitor for one week achieved a total CME regression with recovery of a normal macular and foveal architecture. Conclusions: Surgery-induced CME may occur following stand-alone microinvasive glaucoma surgery (MIGS) such as GATT. It would be worthwhile to conduct studies to explore whether the prophylactic use of NSAID and corticosteroids is justified.
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Glaucoma de Ángulo Abierto , Edema Macular , Hipertensión Ocular , Trabeculectomía , Corticoesteroides/efectos adversos , Anciano , Antiinflamatorios no Esteroideos , Femenino , Estudios de Seguimiento , Glaucoma de Ángulo Abierto/complicaciones , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/cirugía , Gonioscopía , Humanos , Presión Intraocular , Edema Macular/etiología , Estudios Retrospectivos , Trabeculectomía/efectos adversos , Trabeculectomía/métodosRESUMEN
Full-thickness macular hole is a rare complication of macular telangiectasia type 2, and its treatment is still controversial. A patient with a full-thickness macular hole secondary to macular telangiectasia type 2 underwent vitreoretinal surgery with a plasma rich in growth factors membrane in the macular hole. At the sixth month of follow-up, anatomical and functional improvements were achieved, with no adverse effects. Plasma rich in growth factors is a new option, with advantages due to its biological properties that achieves good results in terms of safety and effectiveness in the surgical treatment of macular hole.
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Perforaciones de la Retina , Telangiectasia Retiniana , Humanos , Perforaciones de la Retina/etiología , Perforaciones de la Retina/cirugía , Telangiectasia Retiniana/complicaciones , Telangiectasia Retiniana/terapia , Vitrectomía/métodosRESUMEN
In order to understand the gas-phase hydrogen abstraction reaction between O(3P) and silane we began by developing the first full-dimensional analytical potential energy surface, named PES-2022. It is basically a valence bond function augmented with molecular mechanic terms describing in an intuitive way stretching and bending nuclei motions, and it is fitted to high level ab initio calculations. The surface presents continuous and smooth behaviour, with analytical first energy derivatives, on which the hydrogen atoms in silane are permutationally symmetric. Based on PES-2022, a kinetics study was performed using the variational transition-state theory with multidimensional tunnelling corrections in the temperature range of 300-1000 K. We observed that experimental and theoretical results show widely spread results, both in absolute value and temperature dependence, possibly because they include the reactivity from both O(3P) and O(1D) electronic states, which present different mechanisms and multiple channels. When the comparison is performed on the same footing, O(3P) + SiH4 â HO + SiH3, the present results agree with Ding and Marshall's experiments and with Zhang et al.'s theoretical rate constants. The kinetic isotope effects (KIEs) reproduced the only experimental value, improving previous theoretical results. Finally, a dynamics study was performed on PES-2022 using quasi-classical trajectory calculations under two different initial conditions, at fixed room temperature and at a fixed collision energy of 8.0 kcal mol-1. In the first case, the available energy deposited as HO(v) vibration was 47%, with population inversion, P(v = 0)/P(v = 1) = 11/89%, reproducing the experimental evidence. In the second case, the experimental product translational distribution was reasonably simulated, while the angular product distribution presented opposite behaviour, backward versus forward. On analysing this discrepancy, we found that while in the present work the O(3P) + SiH4 reaction was reported, in the experiment both O(3P) and O(1D) electronic states are reported. So, the comparison was not performed on the same footing. In sum, agreement of the present results with experiments permits us to be reasonably optimistic about the quality and accuracy of the new PES, and at the same time to highlight the fact that theory/experiment comparisons must be performed on the same footing.
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El agujero macular de espesor total es una complicación rara de la telangiectasia macular tipo 2, y su tratamiento es aún controvertido. Una paciente con esta entidad fue llevada a cirugía vitreorretiniana con aplicación de membrana de plasma rico en factores de crecimiento sobre el agujero macular. Al sexto mes de cirugía se logró mejoría anatómica y funcional, sin efectos adversos asociados. El plasma rico en factores de crecimiento es una alternativa nueva en el tratamiento quirúrgico del agujero macular atípico y/o persistente, que logra buenos resultados en términos de seguridad efectividad, debido a sus propiedades biológicas (AU)
Full-thickness macular hole is a rare complication of macular telangiectasia type 2, and its treatment is still controversial. A patient with a full-thickness macular hole secondary to macular telangiectasia type 2 underwent vitreoretinal surgery with a plasma rich in growth factors membrane in the macular hole. At the sixth month of follow-up, anatomical and functional improvements were achieved, with no adverse effects. Plasma rich in growth factors is a new option, with advantages due to its biological properties that achieves good results in terms of safety and effectiveness in the surgical treatment of macular holey (AU)
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Humanos , Femenino , Anciano , Perforaciones de la Retina/etiología , Perforaciones de la Retina/cirugía , Telangiectasia Retiniana/complicaciones , Cirugía Vitreorretiniana/métodos , Factores de Crecimiento Transformadores/administración & dosificación , Plasma , Resultado del TratamientoRESUMEN
Objetivo Publicar las manifestaciones oculares en paciente con leucemia. Métodos Estudio observacional analítico de corte transversal, en pacientes con manifestaciones oculares por leucemia. Resultados Se evaluaron 14 ojos de 8 pacientes (5 mujeres y 3 varones) con leucemia. La edad promedio al diagnóstico de leucemia fue de 43 años (31-76 años). Seis ojos correspondían a pacientes con leucemia mieloide aguda (LMA), 4 ojos a pacientes con leucemia linfoide aguda (LLA), 2 ojos a pacientes con leucemia mieloide crónica (LMC) y 2 ojos a pacientes con leucemia de células peludas (LCP). Los hallazgos oculares primarios fueron: invasión coroidea en 12 ojos (85,7%), infiltración retiniana en 4 ojos (28,6%) y desórdenes neuroftalmológicos en 4 ojos (28,6%). La agudeza visual promedio mejoró de 0,689 a 0,449 logMAR (p 0,012) luego del tratamiento con quimioterapia sistémica e intratecal. De los 8 pacientes, 4 murieron debido a complicaciones de su enfermedad. Conclusiones Este es el primer artículo de múltiples manifestaciones oculares secundaria a leucemia en una población colombiana. Es importante tener en cuenta que este tipo de manifestaciones hacen parte de los síndromes de enmascaramiento por lo tanto es primordial hacer un diagnóstico y manejo precoz ya que en ocasiones está en riesgo la vida del paciente (AU)
Objective To report the ocular manifestations in patients with leukaemia. Methods This is a retrospective, descriptive and observational study in patients with ocular manifestations of leukaemia. Results A total of 14 eyes were evaluated corresponding to 8 patients (5 women and 3 men) with ocular manifestations of leukaemia. The mean age at diagnosis was 43 years (31-76 years). Six eyes corresponded to patients with acute myeloid leukaemia (AML), four eyes to acute lymphoid leukaemia (ALL), two eyes to chronic myeloid leukaemia (CML), and the remaining two belonged to patients with hairy cell leukaemia (HCL). The primary ocular findings were choroidal invasion in 12 eyes (85.7%), retinal infiltration in 4 eyes (28.6%), and neuro-ophthalmic disorders in 4 eyes (28.6%). The mean visual acuity improved from 0.689 to 0.449 (logMAR) (P=.012) after the systemic and intrathecal chemotherapy. Of the eight patients, four died from systemic complications of the underlying disease. Conclusions This is the first report of multiple ocular manifestations secondary to leukaemia in a Colombian population. It is important to keep in mind that this disease is included within the masquerade syndromes and that the ophthalmological findings that, while subtle, can also be devastating and be signs of a life-threatening disease (AU)
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Leucemia/complicaciones , Oftalmopatías/etiología , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Colombia , Estudios Transversales , Agudeza VisualRESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) of the ST1-SCCmecIV lineage has been associated with community-acquired (CA) infections in North America and Australia. In Brazil, multi-drug resistant ST1-SCCmecIV MRSA has emerged in hospital-associated (HA) diseases in Rio de Janeiro. To understand these epidemiological differences, genomic and phylogenetic analyses were performed. In addition, virulence assays were done for representative CA - and HA-MRSA strains. Despite the conservation of the virulence repertoire, some genes were missing in Brazilian ST1-SCCmecIV including lukSF-PV, fnbB, and several superantigen-encoded genes. Additionally, CA-MRSA lost the splDE while HA-MRSA strains conserved the complete operon. Most of these variable genes were located in mobile genetic elements (MGE). However, conservation and maintenance of MGEs were often observed despite the absence of their associated virulence markers. A Bayesian phylogenetic tree revealed the occurrence of more than one entrance of ST1 strains in Rio de Janeiro. The tree shape and chronology allowed us to infer that the hospital-associated ST1-SCCmecIV from Brazil and the community-acquired USA400 from North America are not closely related and that they might have originated from different MSSA strains that independently acquired SCCmecIV cassettes. As expected, representatives of ST1 strains from Brazil showed lower cytotoxicity and a greater ability to survive inside human host cells. We suggest that Brazilian ST1-SCCmecIV strains have adapted to the hospital setting by reducing virulence and gaining the ability to persist and survive inside host cells. Possibly, these evolutionary strategies may balance the biologic cost of retaining multiple antibiotic resistance genes.
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Infecciones Comunitarias Adquiridas/microbiología , Infección Hospitalaria/microbiología , Evolución Molecular , Genoma Bacteriano , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Infecciones Estafilocócicas/microbiología , Teorema de Bayes , Genómica , Genotipo , Humanos , Staphylococcus aureus Resistente a Meticilina/clasificación , Filogenia , Virulencia , Factores de Virulencia/genéticaRESUMEN
Full-thickness macular hole is a rare complication of macular telangiectasia type 2, and its treatment is still controversial. A patient with a full-thickness macular hole secondary to macular telangiectasia type 2 underwent vitreoretinal surgery with a plasma rich in growth factors membrane in the macular hole. At the sixth month of follow-up, anatomical and functional improvements were achieved, with no adverse effects. Plasma rich in growth factors is a new option, with advantages due to its biological properties that achieves good results in terms of safety and effectiveness in the surgical treatment of macular hole.
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OBJECTIVE: To report the ocular manifestations in patients with leukaemia. METHODS: This is a retrospective, descriptive and observational study in patients with ocular manifestations of leukaemia. RESULTS: A total of 14 eyes were evaluated corresponding to 8 patients (5 women and 3 men) with ocular manifestations of leukaemia. The mean age at diagnosis was 43 years (31-76 years). Six eyes corresponded to patients with acute myeloid leukaemia (AML), four eyes to acute lymphoid leukaemia (ALL), two eyes to chronic myeloid leukaemia (CML), and the remaining two belonged to patients with hairy cell leukaemia (HCL). The primary ocular findings were choroidal invasion in 12 eyes (85.7%), retinal infiltration in 4 eyes (28.6%), and neuro-ophthalmic disorders in 4 eyes (28.6%). The mean visual acuity improved from 0.689 to 0.449 (logMAR) (P=.012) after the systemic and intrathecal chemotherapy. Of the eight patients, four died from systemic complications of the underlying disease. CONCLUSIONS: This is the first report of multiple ocular manifestations secondary to leukaemia in a Colombian population. It is important to keep in mind that this disease is included within the masquerade syndromes and that the ophthalmological findings that, while subtle, can also be devastating and be signs of a life-threatening disease.
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A new analytical potential energy surface was developed for the first time for the nine-body O(3P) + C2H6 hydrogen abstraction reaction, named PES-2020, which was fitted to explicitly-correlated high-level electronic structure calculations. This surface simulates the topography of the reactive system, from reactants to products, OH(v,j) + C2H5. The adiabatic energy of reaction, ΔHr(0 K) = -2.33 kcal mol-1, reproduces the experimental evidence, and the barrier height, 10.70 kcal mol-1, agrees with the ab initio calculations used as input. In addition, an intermediate complex in the exit channel is observed, which is stabilized with respect to the products of the reaction. Based on PES-2020 a dynamics study was carried out, where quasi-classical trajectory calculations were performed for collision energies in the range of 7.0-60.0 kcal mol-1, which covers high collision energy regions. The reaction cross section increases with collision energy; the largest fraction of available energy is deposited as translational energy (44-66%), and the scattering distribution evolves from backward to forward with collision energy. These findings reproduce previous theoretical calculations using electronic structure calculations of lower levels. However, where these previous studies failed, viz. in rotational and vibrational OH(v,j) distributions, PES-2020 reproduces practically quantitatively the experimental evidence, i.e., cold vibration and rotation, the rotational distribution peaking at j = 1-3 depending on the collision energy. In sum, this behaviour is typical of gas-phase hydrogen abstraction reactions with direct mechanism and high reaction barrier.
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In pursuit of the ideal photocatalyst, cheap and stable semiconductor TiO2 is considered to be a good choice if one is able to reduce its band gap and decrease the recombination rate of charge carriers. The approach that offers such improvements for energy conversion applications is the modification of TiO2 with nitrogen and noble metals. However, the origin of these improvements and possibilities for further design of single-atom catalysts are not always straightforward. To shed light on the atomic-scale picture, we modeled the nitrogen-doped (001) anatase TiO2 surface as a support for palladium and platinum single-atom deposition. The thermodynamics of various synthesis routes for Pd/Pt deposition and nitrogen doping is considered based on density functional theory (DFT)-calculated energies, highlighting the effect of nitrogen doping on metal dimer formation and metal-support interaction. XPS analysis of the valence band of the modified TiO2 nanocrystals, and the calculated charge transfer and electronic structure of single-atom catalysts supported on the (001) anatase TiO2 surface provide an insight into modifications occurring in the valence zone of TiO2 due to nitrogen doping and Pd/Pt deposition at the surface. DFT results also show that substitutional nitrogen doping significantly increases metal-support interaction, while interstitial nitrogen doping promotes only Pt-support interaction.
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To describe the gas-phase hydrogen abstraction reaction between the hydroxyl radical and the ethane molecule, an analytical full-dimensional potential energy surface was developed within the Born-Oppenheimer approximation. This reactive process is a ten-body system with 24 degrees of freedom, which represents a theoretical challenge. The new surface, named PES-2020, presents low barrier, 3.76 kcal mol-1, high exothermicity, -16.20 kcal mol-1, and intermediate complexes in the entrance and exit channels. To test the quality and accuracy of the analytical surface several stringent tests were performed and, in general, PES-2020 reasonably simulates the theoretical information used as input, it is a continuous and smooth potential, without spurious minima, it presents great versatility and a reasonable description of this ten-body reaction. Based on this surface, an exhaustive kinetics and dynamics study was performed with a double objective: to analyze the capacity of the new surface to simulate the experimental evidence, and to help understand the mechanism of reaction and the role of the ethyl group in the reaction. In the kinetics study, three approaches were used: variational transition-state theory with multidimensional tunnelling (VTST/MT), ring polymer molecular dynamics (RPMD) and quasi-classical trajectory (QCT) results, in the temperature range 200-2000 K. There is general agreement between the three approaches and they reasonably simulate the experimental behaviour, which gives confidence to the fitness of the new surface to describe the system. In the dynamics study, QCT calculations were performed at 298 K for a direct comparison with the only experimental result reported. We found that ethyl fragment presents a noticeable internal energy (â¼20%) and so cannot be considered as a spectator. The water product vibrational energy is reasonably reproduced, though when a level-by-level distribution is analyzed the agreement is only qualitative.
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AIM OF THE STUDY: To present our results with transanal irrigation (TAI) for management of fecal incontinence and fecal constipation without response to other treatments. METHODS: Retrospective study of patients with fecal constipation and/or fecal incontinence treated with TAI between 2013 and 2017. A Rintala questionnaire(1) was carried out comparing pre and post-treatment results. This study was approved by the ethical committee. MAIN RESULTS: Twenty-five patients were included with a median age of 13 years old (range 6-44 years). Nineteen patients had spinal pathology (76%), four colorectal surgery (16%) and two functional constipation (8%). They presented fecal incontinence in 20% of cases, 12% of fecal constipation and 68% both conditions. After a mean follow-up of 1.5 years (1 month-4 years), 52% of the patients abandoned the treatment. The mean Rintala score was 6.8±4 before treatment, and after, resulted to 11.42±2.75 (p=0.001). The main complications throughout the treatment were pain (68%) and balloon leaks (28%). The patients declared as cause of treatment cessation: reduced mobility (15%), fear or misinformation (32%) and pain (76%). All patients with reduced mobility (n=3) left treatment, versus 45% (n=12) of the patients that had full mobility (p=0.17, OR 8.3 [IC95% 0.3-38]). Complementary treatments such as laxatives, enemas or digital extraction were abandoned in 55% of the patients. CONCLUSIONS: Using TAI seems to improve quality of life in patients with fecal constipation and fecal incontinence refractory compared to other treatments. Our abandonment rate was higher than expected, so we believe it is necessary to create a support group to improve follow-ups.
OBJETIVOS: Presentar nuestros resultados con el uso del irrigador transanal (IT) en el manejo intestinal de pacientes con incontinencia fecal o estreñimiento sin respuesta a otros tratamientos. METODOS: Estudio retrospectivo de pacientes con estreñimiento y/o incontinencia fecal refractaria tratados con IT (2013-2017) con el sistema Peristeen® (Coloplast). Se realizó cuestionario Rintala(1), comparando resultados pre y postratamiento. La realización del estudio fue aprobada por el comité de investigación clínica. RESULTADOS: Fueron incluidos en el estudio veinticinco pacientes, mediana de edad 13 años (6-44 años), cuatro no localizables. Diecinueve presentaban patología medular (76%), cuatro cirugías colorrectales (16%) y dos estreñimiento funcional (8%). El 20% aquejaba incontinencia, 12% estreñimiento y 68% ambas condiciones. Tras una mediana de seguimiento de 1,5 años (1 mes-4 años), el 52% abandonó el tratamiento. La puntuación media pretratamiento fue 6,8±4, frente a 11,42±2,75 tras su empleo (p=0,001), disminuyendo el número de escapes con repercusión positiva en actividades diarias. Las complicaciones principales fueron dolor (68%) y expulsión del balón (28%). Refirieron como causa de abandono: dificultad de uso por movilidad reducida (15%), miedo o desinformación (32%) y dolor (76%). El 100% de pacientes con movilidad reducida (n=3) abandonó el tratamiento, frente al 45% (n=12) en el resto (p=0,17, OR 8.3 [IC95% 0,3-38]). El 55% de los pacientes dejaron de utilizar laxantes, enemas o extracción digital. CONCLUSIONES: El uso de IT parece mejorar la calidad de vida en pacientes con estreñimiento e incontinencia de causa orgánica refractaria. La tasa de abandono fue mayor de la esperada, por lo que creemos necesaria la creación de un grupo de apoyo que mejore el seguimiento.
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Estreñimiento/terapia , Incontinencia Fecal/terapia , Adolescente , Adulto , Niño , Estreñimiento/etiología , Enema/efectos adversos , Enema/métodos , Miedo , Femenino , Estudios de Seguimiento , Humanos , Laxativos/uso terapéutico , Masculino , Limitación de la Movilidad , Dolor Asociado a Procedimientos Médicos/etiología , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Pronóstico , Calidad de Vida , Estudios Retrospectivos , Encuestas y Cuestionarios , Irrigación Terapéutica/efectos adversos , Irrigación Terapéutica/métodos , Irrigación Terapéutica/psicología , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJETIVE: To evaluate long-term renal function and morbimortality in non-syndromic Wilms tumor (WT) survivors. METHODS: Retrospective study about WT patients treated in 1993-2017, according to SIOP protocols. Mortality, glomerular filtration rate (GFR), prevalence of hypertension and requirement of dialysis and renal transplant were evaluated. Chronic kidney disease (CKD) was defined as GFR <90 ml/min/1.73 m2. RESULTS: Thirty-nine children were treated in the 25 analyzed years. Median time of follow-up was 6 years (0.5-21 years). 48% (19 patients) debuted with stage I or II. Four cases had high-grade histo-logy. Mortality rate was 10%. GFR data were found in 37 patients. Chronic kidney disease (grade I-II) turned up in 6 patients (16%). No patient required renal replacement therapy or renal transplant. 16% of patients developed CKD in both unilateral and bilateral WT, (p>0.05); OR 1.04 (IC 95% 0.09-10.9). Identical results were obtained comparing patients treated with or without radiotherapy (16%). Children with stage I-III had CKD in 11% vs. 40% of patients with stage IV (p=0.12); OR 5.3 (IC 95% 0.61-45). None of them presented hypertension in addition. CONCLUSIONS: In the current study the prevalence of CKD was low but not negligible, although no patients required renal replacement therapy or renal transplant. Bilateral renal involvement and radiotherapy were not associated with CKD development. Metastatic disease determines a higher risk of CKD.
OBJETIVOS: Evaluar la función renal y la morbimortalidad a largo plazo, en supervivientes de tumor de Wilms (TW) no sindrómico. MATERIAL Y METODOS: Estudio retrospectivo de pacientes con TW entre 1993-2017 tratados según protocolos SIOP. Evaluamos mortalidad, filtrado glomerular (FG), prevalencia de hipertensión arterial (HTA), necesidad de diálisis y trasplante renal. Se definió enfermedad renal crónica (ERC) como FG <90 ml/min/1,73 m2. RESULTADOS: En los 25 años analizados se trataron 39 pacientes con edad media diagnóstica de 3,6 años (0,3-11 años). Mediana de seguimiento 6 años (0,5-21 años). El 48% (19 pacientes) debutaron con estadio I o II. Cuatro pacientes presentaron histología de alto riesgo (10%). La mortalidad fue del 10%. El 16% (6 pacientes) desarrolló ERC (grados I-II). Ningún paciente precisó terapia renal sustitutoria (TRS) o trasplante. La presencia de ERC tanto en enfermedad unilateral como bilateral fue del 16%, p>0,05; OR 1,04 (IC 95% 0,09-10,9). Se obtuvieron idénticos resultados (16%) comparando pacientes que recibieron radioterapia frente a aquellos que no. Los pacientes en estadio I, II y III presentaron una prevalencia de ERC del 11% vs. 40% en estadio IV (p=0,12); OR 5,3 (IC 95% 0,61-45). Ningún paciente asoció HTA crónica. CONCLUSIONES: En el presente estudio la prevalencia de ERC en supervivientes de TW no sindrómico es baja pero no desdeñable, aunque ninguno precisó trasplante renal o TRS. La presencia de enfermedad bilateral y la radioterapia no se asociaron al desarrollo de ERC. La enfermedad metastásica condiciona un riesgo mayor de ERC.
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Supervivientes de Cáncer , Neoplasias Renales/fisiopatología , Riñón/fisiopatología , Tumor de Wilms/fisiopatología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Lactante , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Masculino , Prevalencia , Insuficiencia Renal Crónica/epidemiología , Estudios Retrospectivos , Tumor de Wilms/mortalidad , Tumor de Wilms/patologíaRESUMEN
AIM OF THE STUDY: mTOR inhibitors are being used to treat complex vascular anomalies (VA) without response to conventional treatments. We report our results in pediatric patients treated with sirolimus. METHODS: Retrospective review of patients treated with sirolimus between 2014 and 2017, analyzing vascular anomaly type, treatment response and complications. Treatment protocol included patients with complex vascular anomalies, after signing the informed consent. The initial dose was 0.8 mg/m2/12 h, verifying plasmatic levels. Favorable response was defined both in clinical and radiological terms. MAIN RESULTS: Sirolimus was employed in nine patients, median age 14 months old (1 month-14 years), 66% girls. Five complex micro-cystic lymphatic malformations (LM), one multifocal lynphangioendotheliomatosis with thrombocytopenia, one kaposiform lymphangiomatosis, one lymphatic-venous malformation and one kaposiform hemangioendothelioma (KHE) were treated. Median treatment was 4 months (IQR 2-18 months). Resolution or improvement was objectified in four patients (44%). KHE patient presented complete resolution after two months of treatment. Two patients with micro-cystic LM and the one with lymphatic-venous malformation improved after a median treatment of three months. Two patients presented rebound effect after discontinuing treatment. Three patients had hypertransaminasemia and hypercholesterolemia without requiring medical treatment. CONCLUSION: Sirolimus presented mild effects for treatment of complex VA in our study, but was highly resolutive at KHE.
OBJETIVOS: Los inhibidores mTOR se están utilizando para el tratamiento de anomalías vasculares (AV) complejas sin respuesta a tratamientos convencionales. Presentamos nuestros resultados en pacientes pediátricos tratados con sirolimus. METODOS: Análisis retrospectivo de pacientes tratados con Sirolimus, entre 2014 y 2017, describiendo el tipo de anomalía vascular, respuesta al tratamiento y complicaciones derivadas de su empleo. Se incluyeron pacientes con anomalías vasculares complejas, tras firma del consentimiento informado y con dosis inicial de 0,8 mg/m2/12 horas, monitorizando niveles plasmáticos. Se definió respuesta favorable tanto en términos clínicos como radiológicos. RESULTADOS: Recibieron sirolimus 9 pacientes, mediana de edad de 14 meses (RIQ: 1 mes-14 años). El 66% fueron niñas. Se trataron 5 malformaciones linfáticas (ML) microquísticas complejas (en algunas como coadyuvante a otros tratamientos), 1 linfangioendoteliomatosis multifocal con trombopenia, 1 linfangiomatosis kaposiforme, 1 malformación mixta veno-linfática, 1 hemangioendotelioma kaposiforme (HEK). Mediana de tratamiento: 4 meses (2-18 meses). En 6 pacientes (66%) se objetivó resolución o mejoría de las lesiones. El paciente con HEK mostró resolución completa tras 2 meses de tratamiento. En dos pacientes con ML microquística y en el paciente con malformación mixta, se apreció mejoría clínica y disminución del tamaño de las lesiones tras una mediana de tratamiento de 3 meses. Se apreció efecto rebote en dos ML al suspender el tratamiento. Tres pacientes presentaron hipertransaminasemia e hipercolesterolemia, sin precisar tratamiento médico. CONCLUSIONES: En nuestro estudio, objetivamos que el sirolimus tuvo una eficacia moderada en el tratamiento de AV complejas, pero fue resolutivo en el HEK.
Asunto(s)
Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Malformaciones Vasculares/tratamiento farmacológico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Sirolimus/farmacología , Resultado del Tratamiento , Malformaciones Vasculares/fisiopatologíaRESUMEN
A pivotal event in the evolutionary path of methicillin-resistant Staphylococcus aureus (MRSA) is the acquisition of the staphylococcal cassette chromosome mec (SCCmec) element carrying the mecA gene, the determinant of methicillin resistance. Community-acquired (CA) MRSA is commonly associated with skin/soft tissue infections, and doxycycline is one of the drug choices for this purpose. Doxycycline resistance is associated with the acquisition of the tetK gene carried by the S. aureus plasmid pT181, which may also be integrated into SCCmec III and V. The aim of this study was to describe a novel SCCmec IV subtype (IVm) carrying tetK and reveal the genetic context of this element. The SCCmec sequence was obtained by whole-genome sequencing of the MRSA strain 2288 (ST1 CA-MRSA) and genomic analysis performed using different bioinformatics tools. A copy of pT181 was found to be integrated in the new SCCmec IVm of the strain 2288. The SCCmec IVm has high nucleotide identity (99%) with SCCmec IVa of the strain MW2, except for the J3 region, where the pT181 - carrying tetK gene - is inserted. Inverted repeats (IRs) flanking pT181 were found in this region, suggesting the occurrence of recombination events. The strain 2288 (spa type t125) shares most of the virulence attributes with MW2 (spa type t128), which is recognized in the past as a cause of severe infections in children in USA. The pattern of branching in the phylogenetic tree depicts a recent common ancestor shared by the 2228 strain and other MRSA from USA, including ERS410852, TCH70, CIG1835, CO-41, MW2, and USA400-0051, but none of them carried pT181. This study also showed that the tetK carried by SCCmec IVm is functional, determining resistance to doxycycline and tetracycline. The potential dissemination of the tetK and mecA genes in the same genetic event by the acquisition of this new SCCmec subtype is of concern for community infections.
RESUMEN
An exhaustive kinetics study was performed for the title reaction using two theoretical approaches: variational transition-state theory and quasi-classical trajectory calculations, based on an original new analytical full-dimensional potential energy surface, named PES-2018, which has been fitted to high-level ab initio calculations. The theoretical results were compared with the available experimental data in the temperature range 189-350 K, a difficult comparison because of experimental controversies about the final rate constants (factor of about two) and on the activation energy (positive and negative values have been reported). There is agreement between the two theoretical approaches, with differences of less than 20%, and with the most recent experiments, with differences of less than 30%. Both theories gave small and positive activation energies, reasonably reproducing the most recent experiments, although they showed less dependence on temperature. To understand the theory/experiment differences, several sources of error were analysed, without discarding experimental uncertainties, such as limitations of the theoretical tools (PES and kinetics approaches), and the manner in which spin-orbit effects were included in the present non-relativistic study. Finally, H/D and 12C/13C kinetics isotope effects were reported for the first time for the title reaction, though unfortunately no experimental data are available for comparison.
RESUMEN
The aim of this study was to unravel the genetic determinants responsible for multidrug (including carbapenems) resistance and virulence in a clinical isolate of Klebsiella quasipneumoniae subsp. similipneumoniae by whole-genome sequencing and comparative analyses. Eighty-three clinical isolates initially identified as carbapenem-resistant K. pneumoniae were collected from nosocomial infections in southeast Brazil. After RAPD screening, the KPC-142 isolate, showing the most divergent DNA pattern, was selected for complete genome sequencing in an Illumina HiSeq 2500 instrument. Reads were assembled into scaffolds, gaps between scaffolds were resolved by in silico gap filling and extensive bioinformatics analyses were performed, using multiple comparative analysis tools and databases. Genome sequencing allowed to correct the classification of the KPC-142 isolate as K. quasipneumoniae subsp. similipneumoniae. To the best of our knowledge this is the first complete genome reported to date of a clinical isolate of this subspecies harboring both class A beta-lactamases KPC-2 and OKP-B-6 from South America. KPC-142 has one 5.2 Mbp chromosome (57.8% G+C) and two plasmids: 190 Kbp pKQPS142a (50.7% G+C) and 11 Kbp pKQPS142b (57.3% G+C). The 3 Kbp region in pKQPS142b containing the blaKPC-2 was found highly similar to that of pKp13d of K. pneumoniae Kp13 isolated in Southern Brazil in 2009, suggesting the horizontal transfer of this resistance gene between different species of Klebsiella. KPC-142 additionally harbors an integrative conjugative element ICEPm1 that could be involved in the mobilization of pKQPS142b and determinants of resistance to other classes of antimicrobials, including aminoglycoside and silver. We present the completely assembled genome sequence of a clinical isolate of K. quasipneumoniae subsp. similipneumoniae, a KPC-2 and OKP-B-6 beta-lactamases producer and discuss the most relevant genomic features of this important resistant pathogen in comparison to several strains belonging to K. quasipneumoniae subsp. similipneumoniae (phylogroup II-B), K. quasipneumoniae subsp. quasipneumoniae (phylogroup II-A), K. pneumoniae (phylogroup I), and K. variicola (phylogroup III). Our study contributes to the description of the characteristics of a novel K. quasipneumoniae subsp. similipneumoniae strain circulating in South America that currently represent a serious potential risk for nosocomial settings.
RESUMEN
Staphylococcus aureus subsp. aureus, commonly referred as S. aureus, is an important bacterial pathogen frequently involved in hospital- and community-acquired infections in humans, ranging from skin infections to more severe diseases such as pneumonia, bacteraemia, endocarditis, osteomyelitis, and disseminated infections. Here, we report the complete closed genome sequence of a community-acquired methicillin-resistant S. aureus strain, USA400-0051, which is a prototype of the USA400 clone.