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Many salamanders can completely regenerate a fully functional limb. Limb regeneration is a carefully coordinated process involving several defined stages. One key event during the regeneration process is the patterning of the blastema to inform cells of what they must differentiate into. Although it is known that many genes involved in the initial development of the limb are re-used during regeneration, the exact molecular circuitry involved in this process is not fully understood. Several large-scale transcriptional profiling studies of axolotl limb regeneration have identified many transcription factors that are up-regulated after limb amputation. Sall4 is a transcription factor that has been identified to play essential roles in maintaining cells in an undifferentiated state during development and also plays a unique role in limb development. Inactivation of Sall4 during limb bud development results in defects in anterior-posterior patterning of the limb. Sall4 has been found to be up-regulated during limb regeneration in both Xenopus and salamanders, but to date it function has been untested. We confirmed that Sall4 is up-regulated during limb regeneration in the axolotl using qRT-PCR and identified that it is present in the skin cells and also in cells within the blastema. Using CRISPR technology we microinjected gRNAs specific for Sall4 complexed with cas9 protein into the blastema to specifically knockout Sall4 in blastema cells only. This resulted in limb regenerate defects, including missing digits, fusion of digit elements, and defects in the radius and ulna. This suggests that during regeneration Sall4 may play a similar role in regulating the specification of anterior-proximal skeletal elements.
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Ambystoma mexicanum , Tipificación del Cuerpo , Extremidades , Regeneración , Factores de Transcripción , Animales , Regeneración/genética , Regeneración/fisiología , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Extremidades/fisiología , Extremidades/embriología , Ambystoma mexicanum/genética , Ambystoma mexicanum/fisiología , Tipificación del Cuerpo/genética , Regulación del Desarrollo de la Expresión Génica/genética , Proteínas Anfibias/genética , Proteínas Anfibias/metabolismoRESUMEN
AIM: Perioperative bladder catheterization is a controversial issue. Most current recommendations are based on data from open surgery extrapolated to enhanced recovery after surgery or fast-track programmes ranging between 24 and 48 h. The aim of this study is to provide a rationale for reducing catheterization time while at the same time avoiding acute urine retention (AUR), in patients undergoing scheduled laparoscopic colon surgery. METHOD: This is a multicentre, prospective, controlled, randomized non-inferiority study of bladder catheter management in patients undergoing scheduled laparoscopic colon surgery, randomized into two groups: experimental (with catheter removal immediately after surgery) and control (with catheter removal 24 h post-surgery). The main outcome will be the development of AUR, and secondary outcomes the development of urinary infection within the first 30 days and hospital stay. Demographic, surgical and pathological variables will also be evaluated, especially the development of adverse effects assessed according to the Clavien scale and the Comprehensive Complication Index. Following the literature, we assume an incidence of AUR of 11% and a margin of non-inferiority (delta) of 8% and estimate that a sample size of 208 patients per group will be required (with an estimated 10% of losses per group). CONCLUSIONS: In this study we try to demonstrate that the bladder catheter can be removed immediately after scheduled laparoscopic colon surgery, without increasing acute urine retention. This measure would offers the benefits of earlier mobilization and reduces catheter-related morbidity.
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Vejiga Urinaria , Retención Urinaria , Humanos , Vejiga Urinaria/cirugía , Estudios Prospectivos , Cateterismo Urinario/efectos adversos , Retención Urinaria/etiología , Catéteres Urinarios/efectos adversos , Colon/cirugíaRESUMEN
BACKGROUND: The surgical treatment of choice for rectal neoplasia is total mesorectal excision (TME). The transanal approach enables a better approach in male and obese patients and/or those with a narrow pelvis and in patients with small tumors. Short-term results are comparable with those for laparoscopy or the open approach, but the medium- and long-term oncological data are sparse. The aim of the present study was to evaluate our early experience with transanal TME (TaTME). METHODS: This was a retrospective study conducted on patients who underwent TaTME at our center between August 2013 and April 2017 with a follow-up ≥ 3 years. Histopathology, complications, mortality, neoplastic recurrence and disease-free survival were analyzed. RESULTS: One hundred patients (68 men and 32 women,, median age 66.8 years [range 29.6-91.2 years]) were included. There were 67 T3 cases (67%) with 74 N0 cases (74%), the mesorectal quality was graded optimal for 87.6% and only 2 cases of radial margin involvement were detected (2%). The median follow-up period was 47.6 months (range 11.8-78.9 months). Eighteen cases of recurrence were diagnosed, of which 3 (3%) recurred locally with an average disease-free period of 43.1 months. Overall survival was 80% and mortality due to progression of disease was 13%. CONCLUSIONS: TaTME is a safe surgical procedure with surgical, anatomopathological and oncological results at 3 years (medium-term) comparable with those for the laparoscopic and open approaches. Better monitoring is required with studies of the long-term functional and quality of life outcomes, i.e., at 5 or 10 years.
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Laparoscopía , Neoplasias del Recto , Cirugía Endoscópica Transanal , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Recto/cirugía , Recto/patología , Estudios Retrospectivos , Calidad de Vida , Complicaciones Posoperatorias/cirugía , Cirugía Endoscópica Transanal/métodos , Tempo Operativo , Neoplasias del Recto/patología , Laparoscopía/métodos , Resultado del TratamientoRESUMEN
Mice deficient in the DNA excision-repair gene Ercc1 (Ercc1∆/-) show numerous accelerated ageing features that limit their lifespan to 4-6 months. They also exhibit a 'survival response', which suppresses growth and enhances cellular maintenance. Such a response resembles the anti-ageing response induced by dietary restriction (also known as caloric restriction). Here we report that a dietary restriction of 30% tripled the median and maximal remaining lifespans of these progeroid mice, strongly retarding numerous aspects of accelerated ageing. Mice undergoing dietary restriction retained 50% more neurons and maintained full motor function far beyond the lifespan of mice fed ad libitum. Other DNA-repair-deficient, progeroid Xpg-/- (also known as Ercc5-/-) mice, a model of Cockayne syndrome, responded similarly. The dietary restriction response in Ercc1∆/- mice closely resembled the effects of dietary restriction in wild-type animals. Notably, liver tissue from Ercc1∆/- mice fed ad libitum showed preferential extinction of the expression of long genes, a phenomenon we also observed in several tissues ageing normally. This is consistent with the accumulation of stochastic, transcription-blocking lesions that affect long genes more than short ones. Dietary restriction largely prevented this declining transcriptional output and reduced the number of γH2AX DNA damage foci, indicating that dietary restriction preserves genome function by alleviating DNA damage. Our findings establish the Ercc1∆/- mouse as a powerful model organism for health-sustaining interventions, reveal potential for reducing endogenous DNA damage, facilitate a better understanding of the molecular mechanism of dietary restriction and suggest a role for counterintuitive dietary-restriction-like therapy for human progeroid genome instability syndromes and possibly neurodegeneration in general.
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Envejecimiento/genética , Restricción Calórica , Reparación del ADN/genética , Dieta Reductora , Inestabilidad Genómica , Animales , Encéfalo/fisiología , Daño del ADN , Proteínas de Unión al ADN/deficiencia , Proteínas de Unión al ADN/genética , Endonucleasas/deficiencia , Endonucleasas/genética , Femenino , Masculino , Ratones , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/prevención & control , Proteínas Nucleares/deficiencia , Proteínas Nucleares/genética , Factores de Transcripción/deficiencia , Factores de Transcripción/genética , TranscriptomaRESUMEN
INTRODUCTION: To end the tuberculosis (TB) epidemic, efficient diagnostic tools are needed. In a previous calibration study, a portable 'point of care' electronic nose device (AeonoseTM ) proved to be a promising tool in a hospital setting. We evaluated this technology to detect TB in an indigenous population in Paraguay. METHODS: A total of 131 participants were enrolled. eNose results were compared with anamnesis, physical examinations, chest radiography and mycobacterial cultures in individuals with signs and symptoms compatible with TB. The eNose analysis was performed in two stages: first, the training with a combination of a previous study population plus 47 participants from the new cohort (total n = 153), and second, the 'blind prediction' of 84 participants. RESULTS: 21% of all participants (n = 131) showed symptoms and/or chest radiography abnormalities suspicious of TB. No sputum samples resulted culture positive for Mycobacterium tuberculosis complex. Only one patient had a positive smell print analysis. In the training model, the specificity was 92% (95% confidence interval (CI): 85%-96%) and the negative predictive value (NPV) was 95%. In the blind prediction model, the specificity and the NPV were 99% (95% CI: 93%-99%) and 100%, respectively. Although the sensitivity and positive predictive value of the eNose could not be assessed in this cohort due to the small sample size, no active TB cases were found during a one year of follow-up period. CONCLUSION: The eNose showed promising specificity and negative predictive value and might therefore be developed as a rule-out test for TB in vulnerable populations.
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Nariz Electrónica , Sistemas de Atención de Punto , Grupos de Población , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/etnología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paraguay , Proyectos Piloto , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Figure 1(b) in [V. F. Gili et al, Opt. Express24, 15965 (2016)10.1364/OE.24.015965] is corrupted and is corrected in this erratum.
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Monocytes play a key role in pathophysiology of antiphospholipid syndrome (APS), nevertheless it is unclear if microRNA expression is associated with particular APS features. Identify whether miR-19b-3p and miR-20a-5p expression in monocytes are associated with hallmarks of the APS. Fifty-seven APS patients and 18 healthy controls were studied. Expression of miR-19b-3p and miR-20a-5p was measured in monocytes by RT-qPCR. Both miR-19b-3p (AUC = 0.835, 95% CI 0.733-0.938; P < 0.001) and miR-20a-5p (AUC = 0.857, 0.757-0.957; P < 0.001) discriminated APS patients from healthy individuals. A cut-off point of 1.98 for miR-19-3p and 2.18 for miR-20a-5p showed that APS patients with low microRNA expression had higher levels of IgM and IgG anticardiolipin antibodies than patients with high microRNA expression. In addition, APS patients with low microRNA expression had higher IgG anti-ß2 glycoprotein I antibody levels than their counterparts with high microRNA expression. Finally, miR-19b-3p and miR-20a-5p expression levels were significantly higher in APS patients using oral anticoagulants. Monocyte expression of miR-19b-3p and miR-20a-5p is low in APS, and patients with the lowest microRNA expression presented the highest levels of antiphospholipid antibodies.
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Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/metabolismo , MicroARNs/metabolismo , Monocitos/metabolismo , Adulto , Síndrome Antifosfolípido/sangre , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Infectious disease coronavirus 2019 (COVID-19) is caused by the SARS-CoV-2 virus, and it mainly affects the upper respiratory tract. The gold standard for its diagnosis is real-time reverse transcription polymerase chain reaction (RT-qPCR) performed on a nasopharyngeal swab. In contrast, testing saliva has significant advantages as a diagnostic method. MATERIAL AND METHODS: We searched for articles evaluating saliva as a diagnostic method for COVID-19 on the PUBMED/MEDLINE, WEB OF SCIENCE, COCHRANE, and SCIELO platforms. We initially found 233 articles and 20 were selected for inclusion following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol: 18 cross-sectional studies and 2 case reports, including 8 from America, 8 from Asia, and 4 from Europe. The studies evaluated the presence of viral RNA, IgG, IgM, and IgA in samples of unstimulated saliva from adults with confirmed or suspected COVID-19. The vast majority of the studies performed RT-qPCR on the saliva samples and compared the results with the gold standard (a nasopharyngeal swab of the same patient). RESULTS: Saliva samples analyzed by RT-qPCR, reverse transcription isothermal amplification (RT-LAMP), spectroscopy, and enzyme-linked immunosorbent assay (ELISA) offer high sensitivity to detect SARS-CoV-2 in the early stages of the disease and among asymptomatic patients as compared to nasopharyngeal swab RT-qPCR. In addition, the self-collection of saliva offers the possibility of receiving telemedicine instructions to carry out the test, reducing the risk of contagion. CONCLUSIONS: The diagnosis of COVID-19 through saliva is sensitive, non-invasive, and is of low risk for the healthcare professionals. However, further studies are recommended to validate its clinical use.
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COVID-19 , Saliva , Adulto , Asia , Estudios Transversales , Europa (Continente) , Humanos , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido Nucleico , SARS-CoV-2 , Sensibilidad y EspecificidadRESUMEN
The lack of naturally occurring resistance to citrus psorosis virus (CPsV) necessitates a transgenic approach for the development of CPsV-resistant citrus. To evaluate the feasibility of conferring resistance to a non-transgenic scion, we have assembled citrus plants by grafting combining a non-transgenic Sweet Orange as scion, CPsV-resistant transgenic Sweet Orange lines expressing intron-hairpin (ihp) RNA derived from the viral coat protein (ihpCP) as interstock, and a non-transgenic citrus as rootstock. We demonstrated that ihpCP-transcripts translocate through the graft from interstock to scion, triggering the silencing of coat protein mRNA target. Two independent CPsV challenge assays showed that expression of ihpCP in the interstock provides resistance against CPsV in the interstock, and different levels of protection in the non-tg scion, depending of the virus delivery site. These results indicated that grafting is a promising biotechnological alternative to protect woody plants against virus infections in vegetative propagated plants.
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Citrus/inmunología , Inmunidad Innata/inmunología , Enfermedades de las Plantas/inmunología , Virus de Plantas/genética , Plantas Modificadas Genéticamente/inmunología , ARN Mensajero/genética , Proteínas Virales/genética , Citrus/genética , Citrus/crecimiento & desarrollo , Citrus/virología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/virología , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/crecimiento & desarrollo , Plantas Modificadas Genéticamente/virologíaRESUMEN
OBJECTIVE: The French national rare gynecological tumor network has been established to improve the quality of care through offering expertise in double reading histological diagnosis, reviewing cases and guiding management of these tumors through specialized multidisciplinary tumor boards and online clinical guidelines (www.ovaire-rare.com). The aim of this study is to evaluate the impact of the development and implementation of this network by assessing the conformity of medical practice with the guidelines concerning the granulosa cell tumors (GCTs). METHODS: This is a French nationwide study, including 463 patients (out of the 639 identified patients) with a definitive diagnosis of GCT between 2011 and 2016. Surgical practices were analyzed for conformity with the current guidelines (www.ovaire-rare.org). Medical records, surgical and pathological reports were systematically analyzed. Total conformity was defined by a conservative (unilateral salpingo-oophorectomy) or radical surgery (hysterectomy and bilateral salpingo-oophorectomy) including surgical staging (omentectomy, peritoneal biopsies and peritoneal cytology) according to the FIGO stage. Partial conformity referred to a conservative or radical surgery without surgical staging and non-conformity was defined as a non-optimal surgery as recommended by the guidelines. RESULTS: Median age at diagnosis was 49 years old (range 10-89). The median size of tumor was 94 mm (range 5-400). Radical surgery was performed in 240 patients (52%); while a fertility-sparing surgery was performed in 98 cases (21%). A surgical staging was performed in 76 cases (16%) and an evaluation of the endometrium in 289 cases (62%). Surgery was fully compliant with the guidelines in 65 patients (14%), partially compliant in 213 patients (46%), non-compliant in 137 patients (30%) and not assessable in 48 cases (10%). A statistically significant difference for compliance was observed in restaging surgery (p < 0,001), radical surgery (p = 0,017) and the period (before or after) of the implementation of the network (p < 0,001). Survival analyses did not allow us to demonstrate a significant difference in overall survival nor in PFS although there was a trend in favor of optimal surgery compared to incomplete/non optimal surgery. CONCLUSION: Surgical management's conformity to the guidelines increases over time from 2011 to 2016. According to this study, the implementation of a national network dedicated to rare gynecologic tumors seems to significantly improve the surgical management of the patients with ovarian granulosa cell tumors.
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Tumor de Células de la Granulosa/diagnóstico , Tumor de Células de la Granulosa/cirugía , Procedimientos Quirúrgicos Ginecológicos/normas , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Estudios de Cohortes , Femenino , Francia/epidemiología , Tumor de Células de la Granulosa/mortalidad , Adhesión a Directriz , Procedimientos Quirúrgicos Ginecológicos/métodos , Procedimientos Quirúrgicos Ginecológicos/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/mortalidad , Enfermedades Raras/diagnóstico , Enfermedades Raras/cirugía , Estudios Retrospectivos , Adulto JovenRESUMEN
A dual ion species plasma expansion scheme from a novel target structure is introduced, in which a nanometer-thick layer of pure deuterium exists as a buffer species at the target-vacuum interface of a hydrogen plasma. Modeling shows that by controlling the deuterium layer thickness, a composite H^{+}/D^{+} ion beam can be produced by target normal sheath acceleration (TNSA), with an adjustable ratio of ion densities, as high energy proton acceleration is suppressed by the acceleration of a spectrally peaked deuteron beam. Particle in cell modeling shows that a (4.3±0.7) MeV per nucleon deuteron beam is accelerated, in a directional cone of half angle 9°. Experimentally, this was investigated using state of the art cryogenic targetry and a spectrally peaked deuteron beam of (3.4±0.7) MeV per nucleon was measured in a cone of half angle 7°-9°, while maintaining a significant TNSA proton component.
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BACKGROUND AND PURPOSE: Patients with acute intracerebral hemorrhage (ICH) pretreated with antithrombotic drugs may have increased early hematoma growth, which would increase mortality risk. The effect of antiplatelet (AP) and vitamin K antagonist (VKA) pretreatment on ultra-early hematoma growth (uHG) and its relationship with mortality in patients with acute supratentorial ICH was analyzed. METHODS: This is an observational retrospective study of a prospective register of 197 ICH patients with first computed tomography (CT) scan taken <6 h from ICH symptom onset. ICH volume was calculated by the ABC/2 formula and uHG by the baseline ICH volume/onset-to-CT time (ml/h) formula. The uHG analysis took into account the patient's pretreatment (none, AP or VKA) and the relationship between uHG and very-early (first 24 h) and 3-month mortality. RESULTS: In the pretreatment group, 50 (25.4%) patients were treated with AP and 37 (18.8%) with VKA. The median (interquartile range 25-75) uHG was 19.7 ml/h (2.9-44.8) for AP pretreated patients, 16.2 ml/h (5.1-42.5) for VKA pretreated patients and 8.4 ml/h (2.4-21.8) for non-pretreated patients, P = 0.019. The uHG was higher in patients with very-early [42.1 ml/h (20.1-79.6)] and total 3-month mortality [28.0 ml/h (15.8-52.5)] compared with survivors [3.9 ml/h (1.5-10.4)], P < 0.0001. Adjusted by ICH severity and previous functional status, uHG was an independent factor related to very-early (P = 0.028) and total 3-month mortality (P = 0.014). CONCLUSIONS: Patients pretreated with antithrombotics have much higher uHG, which would explain the increased mortality in these patients compared to untreated patients.
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Anticoagulantes/uso terapéutico , Antifibrinolíticos/uso terapéutico , Encéfalo/diagnóstico por imagen , Hemorragia Cerebral/diagnóstico por imagen , Hematoma/diagnóstico por imagen , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticoagulantes/farmacología , Antifibrinolíticos/farmacología , Encéfalo/efectos de los fármacos , Hemorragia Cerebral/mortalidad , Femenino , Hematoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/farmacología , Estudios Prospectivos , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND AND PURPOSE: Alcohol overuse (AOu) is considered an important risk factor for spontaneous intracerebral hemorrhage (ICH). The clinical and outcome characteristics of these patients (AOu-ICH) are not well known. METHODS: All patients with ICH admitted to a single university tertiary stroke center were prospectively studied from May 2005 to May 2015. Demographic profiles, radiologic characteristics and clinical outcomes of patients with acute ICH and previous AOu (>40 g/day or >300 g/week) were analyzed. RESULTS: During the study period, 555 patients with spontaneous primary ICH met the inclusion criteria. A total of 81 patients (14.6%) reported AOu (24.3% of men vs. 3.1% of women; P < 0.0001; mean age, 63 years old for AOu vs. 74 years old for non-AOu; P < 0.0001). Of the classic cardiovascular risk factors, only smoking was associated with AOu (63% vs. 12.2% of non-AOu; P < 0.0001). Initial severity and hematoma volume were similar in both groups, with no observed differences in stroke care or in-hospital medical complications. Patients with AOu had worse outcome (modified Rankin Scale score, 3-6 points) than patients without AOu at 3 months [odds ratio (OR), 2.50; 95% confidence interval (CI), 1.32-4.75; P = 0.005] and 12 months (OR, 2.47; 95% CI, 1.23-5.00; P = 0.011). A similar trend was observed at 5 years (OR, 2.48; 95% CI, 0.96-6.39; P = 0.059). CONCLUSIONS: Alcohol overuse was present in 14.6% of patients with ICH, who were predominantly male, smokers and a mean of 11 years younger than the non-AOu group. Despite a lack of differences in initial clinical severity, stroke care and early medical complications, patients with AOu had worse short- and long-term outcomes.
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Alcoholismo/complicaciones , Hemorragia Cerebral/etiología , Accidente Cerebrovascular/etiología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , FumarRESUMEN
BACKGROUND: In children with egg protein allergy (EA), the probability of overcoming the allergy decreases with age, and the possibility of suffering severe adverse reactions as a consequence of dietetic transgressions results in worsened quality of life. One treatment option in such cases is oral immunotherapy (OIT) with foods. METHODS: We present a cohort of children with EA scheduled for OIT with pasteurized raw egg white, describing their clinical and allergic characteristics before the start of OIT. RESULTS: The median age was six years, and 93% of the patients also suffered other allergies (58% asthma and 38.6% allergy to more than two food groups). In the last year, 14.8% had suffered a severe reaction due to dietetic transgression with egg. The median IgE specific of egg white titer was 38.5kU/l. A double-blind placebo-controlled food challenge with cooked egg white was performed, and if the test proved positive, it was repeated with pasteurized raw egg white. The mean symptoms-provoking dose was 1.26g and 0.55g for cooked egg white and raw egg white, respectively. An IgE specific of ovomucoid titer of <2.045kU/l differentiated those patients that tolerated cooked egg white. CONCLUSIONS: OIT with egg is regarded as an option in patients with persistent egg allergy. In the previous challenge test, an IgE specific of ovomucoid titer of <2.045kU/l differentiates those patients that tolerate cooked egg white.
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Hipersensibilidad al Huevo/inmunología , Clara de Huevo/efectos adversos , Administración Oral , Alérgenos/efectos adversos , Alérgenos/inmunología , Niño , Desensibilización Inmunológica , Método Doble Ciego , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. METHODS: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. RESULTS: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). CONCLUSIONS: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/secundario , Neoplasias Esofágicas/tratamiento farmacológico , Unión Esofagogástrica , Nomogramas , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/química , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Ascitis/etiología , Neoplasias Esofágicas/química , Neoplasias Esofágicas/patología , Estado de Salud , Humanos , Recuento de Linfocitos , Persona de Mediana Edad , Clasificación del Tumor , Neutrófilos , Receptor ErbB-2/análisis , Neoplasias Gástricas/química , Neoplasias Gástricas/patología , Tasa de Supervivencia , Trastuzumab/administración & dosificación , Carga Tumoral , Población Blanca , Adulto JovenRESUMEN
Costimulatory inhibitors (i.e. abatacept and belatacept) effectively abrogate T lymphocyte activation and proliferation and have been shown to be effective for disease control in certain autoimmune disorders as well as in preventing allograft rejection in kidney transplantation. Whether such immunomodulatory agents may be useful for the control of autoimmune flares and allograft acceptance, while avoiding the need of additional strong immunosuppressants, has not been shown. Here, we report the first case of a 47-year-old man affected by a serious debilitating form of psoriatic arthritis that presented during the course of a third, high immunological-risk kidney transplantation. Three years after transplantation, the patient benefited by switching from tacrolimus- to belatacept-based therapy, without additional immunosuppression, by showing complete regression of the arthritic symptoms as well as no progression of severe radiological lesions, which leaded to the recovery of disability and functional impairment. Remarkably, the treatment with belatacept in association with mycophenolate mofetil and steroids also provided a stable normal allograft function over time and abrogated the development of de novo circulating donor-specific alloantibodies after 4 years of follow-up.
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Abatacept/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Rechazo de Injerto/prevención & control , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Artritis Psoriásica/inducido químicamente , Rechazo de Injerto/etiología , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
We report on the experimental observation of quasi-phase matching in a homogeneous waveguide. By fabricating a monolithic snake-shaped suspended AlGaAs nanowire on a (001) GaAs wafer, we demonstrate the unraveled version of a χ(2) whispering-gallery-mode microdisk, obtaining second-harmonic generation in the optical telecom wavelength range. With a radius of curvature of 50 µm and four spatial oscillations along the (110) average direction, a splitting of the second-harmonic spectrum occurs around the phase-matching wavelength of the corresponding straight waveguide. This splitting, which increases as the radius of curvature decreases, provides a useful degree of freedom for the design of small-footprint nonlinear photonic devices on-chip.
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Collective phenomena emerging from nonlinear interactions between multiple oscillators, such as synchronization and frequency locking, find applications in a wide variety of fields. Optomechanical resonators, which are intrinsically nonlinear, combine the scientific assets of mechanical devices with the possibility of long distance controlled interactions enabled by traveling light. Here we demonstrate light-mediated frequency locking of three distant nano-optomechanical oscillators positioned in a cascaded configuration. The oscillators, integrated on a chip along a common coupling waveguide, are optically driven with a single laser and oscillate at gigahertz frequency. Despite an initial mechanical frequency disorder of hundreds of kilohertz, the guided light locks them all with a clear transition in the optical output. The experimental results are described by Langevin equations, paving the way to scalable cascaded optomechanical configurations.