134 research outputs found
Establishment of urinary exosome-like vesicles isolation protocol for FHHNC patients and evaluation of different exosomal RNA extraction methods
Molecular and cellular pathophysiological events occurring in the majority of rare kidney diseases remain to be elucidated. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder caused by mutations in either CLDN16 or CLDN19 genes. This disease is characterized by massive urinary wasting of magnesium and calcium, osmosis deregulation and polyuria. Patients with p.G20D homozygous mutation in CLDN19 gene exhibit different progression to kidney failure suggesting that beyond the pathogenic mutation itself, other molecular events are favoring disease progression. Due to the fact that biopsy is not clinically indicated in these patients, urinary exosome-like vesicles (uEVs) can be envisioned as a valuable non-invasive source of information of events occurring in the kidney. Exosome research has increased notably to identify novel disease biomarkers but there is no consensus standardized protocols for uEVs isolation in patients with polyuria. For this reason, this work was aimed to evaluate and refine different uEVs isolation methods based on differential centrifugation, the gold standard method. Characterization by NTA, cryo-TEM and immunoblotting techniques identified the most appropriate protocol to obtain the highest yield and purest uEVs enriched fraction possible from urine control samples and FHHNC patients. Moreover, we tested five different RNA extraction methods and evaluated the miRNA expression pattern by qRT-PCR. In summary, we have standardized the conditions to proceed with the identification of differentially expressed miRNAs in uEVs of FHHNC patients, or other renal diseases characterized by polyuria
Fachadas ligeras
Entre los temas objeto de estudio de la «Union Européenne pour l'agrément technique dans la construction», figura el genérico de «Fachadas ligeras». Los grupos de trabajo de la Asociación, integrados por técnicos especialistas, representan a los Centros de investigación de los diversos países europeos que la forman, donde se realizan los estudios y ensayos, eminentemente científicos y técnicos, los cuales son analizados en común en las llamadas Reuniones «ad-hoc» que vienen celebrándose desde hace unos años, como es sabido, en diferentes ciudades europeas
Expert guidance on the multidisciplinary management of cystinosis in adolescent and adult patients
Clinical recommendations; Cystinosis; Multidisciplinary careRecomendaciones clínicas; Cistinosis; Atención multidisciplinariaRecomanacions clíniques; Cistinosi; Atenció multidisciplinàriaCystinosis, a rare autosomal recessive lysosomal storage disorder, results in an abnormal accumulation of the amino acid cystine in multiple organs and tissues of the body. Renal symptoms typically develop in the first few months of life, with extra-renal manifestations becoming apparent over the next 10–20 years, which require coordinated multidisciplinary care. Here, we describe a consensus-based guidance to support the management of adolescents and adults living with cystinosis. The programme was led by a Steering Committee (SC) of six experts in the management of patients with cystinosis, who identified a list of 15 key questions reflecting the multi-organ effects of cystinosis. An Extended Faculty (EF) of eight additional specialists was invited to answer the questions via an online digital platform using a quasi-Delphi approach. The consolidated answers were summarized into recommendations. Where evidence was lacking, recommendations were developed using collective expert consensus. The EF was asked to agree/disagree with the clinical recommendations. The expert-agreed clinical recommendations provide guidance that considers both renal and extra-renal systems. The topics covered are advice on fertility and family planning, consideration of the nervous, muscular, ophthalmic, cardio-respiratory, endocrine, dermatological and gastrointestinal systems, as well as guidance on dental care, diet, lifestyle, and improving quality of life and psychological well-being. In summary, this work outlines recommendations and a checklist for clinicians with a vision for improving and standardizing the multidisciplinary care for patients with cystinosis.The programme was supported by Chiesi Farmaceutici Spa. Chiesi was not involved in the content or outcomes of the programme which were solely determined by the SC and extended faculty experts
PHYOX2: a pivotal randomized study of nedosiran in primary hyperoxaluria type 1 or 2
Chronic kidney disease; Pediatric nephrology; UrologyMalaltia renal crònica; Nefrologia pediàtrica; UrologiaEnfermedad renal crónica; Nefrología pediátrica; UrologíaNedosiran is an investigational RNA interference agent designed to inhibit expression of hepatic lactate dehydrogenase, the enzyme thought responsible for the terminal step of oxalate synthesis. Oxalate overproduction is the hallmark of all genetic subtypes of primary hyperoxaluria (PH). In this double-blind, placebo-controlled study, we randomly assigned (2:1) 35 participants with PH1 (n = 29) or PH2 (n = 6) with eGFR ≥30 mL/min/1.73 m2 to subcutaneous nedosiran or placebo once monthly for 6 months. The area under the curve (AUC) of percent reduction from baseline in 24-hour urinary oxalate (Uox) excretion (primary endpoint), between day 90–180, was significantly greater with nedosiran vs placebo (least squares mean [SE], +3507 [788] vs −1664 [1190], respectively; difference, 5172; 95% CI 2929–7414; P < 0.001). A greater proportion of participants receiving nedosiran vs placebo achieved normal or near-normal (<0.60 mmol/24 hours; <1.3 × ULN) Uox excretion on ≥2 consecutive visits starting at day 90 (50% vs 0; P = 0.002); this effect was mirrored in the nedosiran-treated PH1 subgroup (64.7% vs 0; P < 0.001). The PH1 subgroup maintained a sustained Uox reduction while on nedosiran, whereas no consistent effect was seen in the PH2 subgroup. Nedosiran-treated participants with PH1 also showed a significant reduction in plasma oxalate versus placebo (P = 0.017). Nedosiran was generally safe and well tolerated. In the nedosiran arm, the incidence of injection-site reactions was 9% (all mild and self-limiting). In conclusion, participants with PH1 receiving nedosiran had clinically meaningful reductions in Uox, the mediator of kidney damage in PH
Fractional corner charges in spin-orbit coupled crystals
We study two-dimensional spinful insulating phases of matter that are protected by time-reversal and crystalline symmetries. To characterize these phases, we employ the concept of corner charge fractionalization: corners can carry charges that are fractions of even multiples of the electric charge. The charges are quantized and topologically stable as long as all symmetries are preserved. We classify the different corner charge configurations for all point groups, and match them with the corresponding bulk topology. For this we employ symmetry indicators and (nested) Wilson loop invariants. We provide formulas that allow for a convenient calculation of the corner charge from Bloch wave functions and illustrate our results using the example of arsenic and antimony monolayers. Depending on the degree of structural buckling, these materials can exhibit two distinct obstructed atomic limits. We present density functional theory calculations for open flakes to support our findings
El cultivo de alpiste (Phalaris canariensis L.)
El alpiste es una gramínea anual, que se cultiva extensivamente en las regiones templadas del mundo para la obtención de sus granos. Es una especie de estación fría, cuyas prácticas de producción, requerimientos y ciclo de cultivo, se asemejan a los de otros cereales invernales como el trigo y la cebada.
Históricamente los granos de alpiste han sido utilizados, casi con exclusividad, en la alimentación de aves ornamentales. Sin embargo, estudios recientes han propuestos otros usos alternativos como la alimentación de animales de cría y la elaboración de alimentos ―libres de gluten‖ para humanos.
Nuestro país cuenta con una larga historia en la producción y comercialización de alpiste, habiendo sido hasta la década de los ochenta su principal productor. En la actualidad se encuentra entre los tres más importantes, siendo Canadá líder indiscutido.
En la Argentina, el cultivo de alpiste se realiza, principalmente, en la regiones centro y sur este de la provincia de Buenos Aires, áreas de influencia de las Facultades de Agronomía del Centro de la Provincia de Buenos Aires y Ciencias Agrarias de la Universidad de Mar del Plata.
Ambas instituciones cuentan con grupos de investigación que llevan más de una década generando conocimientos sobre el cultivo de alpiste, sus prácticas de producción, fisiología y mejoramiento genético.
Quien, por necesidad o curiosidad, se haya interesado en el estudio de esta especie, habrá evidenciado la escasez de información disponible.
Asimismo, habrá observado que gran parte de la información confiable circula a través de publicaciones científicas que en ocasiones son de difícil acceso.
El propósito de este libro es poner a disposición de sus lectores los conocimientos actualizados sobre el alpiste, en el ámbito nacional e internacional, cubriendo aspectos que van desde la taxonomía hasta su comercialización. La obra está destinada a estudiantes, profesionales e investigadores de la agronomía y disciplinas afines. Sin embargo, algunos capítulos, como los que tratan sobre los requerimientos y el manejo del cultivo, han sido escritos con terminología accesible, debido a que contienen información de utilidad para los productores.
Cabe destacar que en la redacción de la obra han participado docentes e investigadores de diferentes ramas de la agronomía, estudiado el cultivo desde sus diversas perspectivas disciplinares
A novel real-time PCR assay for quantitative detection of Campylobacter fetus based on ribosomal sequences
Background: Campylobacter fetus is a pathogen of major concern for animal and human health. The species shows a great intraspecific variation, with three subspecies: C. fetus subsp. fetus, C. fetus subsp. venerealis, and C. fetus subsp. testudinum. Campylobacter fetus fetus affects a broad range of hosts and induces abortion in sheep and cows. Campylobacter fetus venerealis is restricted to cattle and causes the endemic disease bovine genital campylobacteriosis, which triggers reproductive problems and is responsible for major economic losses. Campylobacter fetus testudinum has been proposed recently based on genetically divergent strains isolated from reptiles and humans. Both C. fetus fetus and C. fetus testudinum are opportunistic pathogens for immune-compromised humans. Biochemical tests remain as the gold standard for identifying C. fetus but the fastidious growing requirements and the lack of reliability and reproducibility of some biochemical tests motivated the development of molecular diagnostic tools. These methods have been successfully tested on bovine isolates but fail to detect some genetically divergent strains isolated from other hosts. The aim of the present study was to develop a highly specific molecular assay to identify and quantify C. fetus strains. Results: We developed a highly sensitive real-time PCR assay that targets a unique region of the 16S rRNA gene. This assay successfully detected all C. fetus strains, including those that were negative for the cstA gene-based assay used as a standard for molecular C. fetus identification. The assay showed high specificity and absence of cross-reactivity with other bacterial species. The analytical testing of the assay was determined using a standard curve. The assay demonstrated a wide dynamic range between 102 and 107 genome copies per reaction, and a good reproducibility with small intra- and inter-assay variability. Conclusions: The possibility to characterize samples in a rapid, sensitive and reproducible way makes this assay a good option to establish a new standard in molecular identification and quantification of C. fetus species
Aspectos clínicos y epidemiológicos de pacientes con trombofilia primaria. Cardiocentro “Ernesto Che Guevara”. 2011- 2014
Introducción: La trombofilia primaria es una enfermedad poco frecuente y sub-diagnosticada.Objetivo: Caracterizar clínica y epidemiológicamente los pacientes con trombofilia primaria atendidos en el Cardiocentro Ernesto Che Guevara, en el período de septiembre del 2011 a febrero del 2014.Diseño Metodológico: Se realizó un estudio observacional-descriptivo-transversal con búsqueda de información retrospectiva en los pacientes atendidos en la consulta de Trombofilia del Cardiocentro Ernesto Che Guevara, durante el período de septiembre del 2011 a febrero del 2014.Resultados: La edad media de los pacientes fue 33 años. Los factores de riesgo de mayor frecuencia determinados fueron hipertensión arterial en el 19,1 %, obesidad con igual frecuencia y en el 17 % la cirugía mayor. En el 98,1 % de los pacientes el primer episodio trombótico objetivado ocurrió antes de los 50 años, el 75,5 % presentó trombosis recurrentes y en el 47,2 % no se detectó factor precipitante. Las localizaciones clínicas de trombosis más frecuentes fueron trombosis venosa profunda (TVP) en extremidades inferiores en el 57 % y trombosis cerebral en el 28 % de los pacientes. El 45,2% de los pacientes presentaron trombofilia primaria, de estos en el 37,5 % se determinó más de un factor trombofílico.Conclusiones: Se determinó trombofilia primaria en casi la mitad de los pacientes involucrados en el estudio, el déficit de proteína S fue la causa predominante, se identificó trombofilia combinada, siendo la asociación más frecuente el déficit de proteína C y S. ABSTRACTIntroduction: Primary thrombophilia is a rare and under-diagnosed disease.Objective: To characterize clinically and epidemiologically patients with primary thrombophilia treated at the Cardiology Center Ernesto Che Guevara, in the period between September 2011 to February 2014.Materials and Methods: A cross-sectional, descriptive-observational study with retrospective data search in patients treated at the Cardiology Thrombophilia of Ernesto Che Guevara, during the period September 2011 to February 2014.Results: The mean age of patients was 33 years. The risk factors most frequently identified were hypertension in 19.1%, and obesity with equal frequency in 17% of major surgery. In 98.1% of patients the first thrombotic event occurred before the age of 50 and 75.5% had recurrent thrombosis. The more frequent clinical sites were deep vein thrombosis (DVT) of the lower extremities in 57% and cerebral thrombosis in 28% of patients. 45.2% of patients had primary thrombophilia; in 37.5% of these was determined more than one thrombophilic factor.Conclusions: Primary thrombophilia was found in almost half of the patients involved in the study, protein S deficiency was the predominant cause, and combined thrombophilia was identified, being the most frequent, the association of protein C and S deficiency
Spectroscopic evidence for topological band structure in FeTeSe
FeTeSe(FTS) occupies a special spot in modern condensed
matter physics at the intersections of electron correlation, topology, and
unconventional superconductivity. The bulk electronic structure of FTS is
predicted to be topologically nontrivial thanks to the band inversion between
the and bands along -. However, there remain debates
in both the authenticity of the Dirac surface states (DSS) and the experimental
deviations of band structure from the theoretical band inversion picture. Here
we resolve these debates through a comprehensive ARPES investigation. We first
observe a persistent DSS independent of . Then, by comparing FTS with FeSe
which has no band inversion along -, we identify the spectral weight
fingerprint of both the presence of the band and the inversion between
the and bands. Furthermore, we propose a reconciling band
structure under the framework of a tight-binding model preserving crystal
symmetry. Our results highlight the significant influence of correlation on
modifying the band structure and make a strong case for the existence of
topological band structure in this unconventional superconductor
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