RESUMEN
For the first time to our knowledge, we demonstrate that whole angiosperm individuals can survive gut passage through birds, and that this occurs in the field. Floating plants of the genus Wolffia are the smallest of all flowering plants. Fresh droppings of white-faced whistling duck Dendrocygna viduata ( n = 49) and coscoroba swan Coscoroba coscoroba ( n = 22) were collected from Brazilian wetlands. Intact Wolffia columbiana were recovered from 16% of D. viduata and 32% of Coscoroba samples (total = 164 plantlets). The viability of plants was tested, and asexual reproduction was confirmed. Wolffia columbiana is an expanding alien in Europe. Avian endozoochory of asexual angiosperm propagules may be an important, overlooked dispersal means for aquatic plants, and may contribute to the invasive character of alien species.
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Araceae/fisiología , Patos/fisiología , Dispersión de las Plantas , Animales , Organismos Acuáticos , Brasil , Heces , Especies Introducidas , Reproducción AsexuadaRESUMEN
To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.
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Moléculas de Adhesión Celular/genética , Función Ejecutiva/fisiología , Anciano , Anciano de 80 o más Años , Moléculas de Adhesión Celular/fisiología , Cognición/fisiología , Estudios de Cohortes , Femenino , Estudios de Asociación Genética , Variación Genética/genética , Estudio de Asociación del Genoma Completo , Genómica , Humanos , Intrones , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Polimorfismo de Nucleótido Simple , Población Blanca/genética , Ácido gamma-AminobutíricoRESUMEN
We analyzed lymphocyte subpopulations and cytokines 3 months after allogeneic hematopoietic stem cell transplantation aiming to identify predictive cellular and serum markers for chronic graft-versus-host disease (cGVHD). Samples of 49 patients (pts) (no cGVHD (n = 14), subsequent quiescent onset (n = 16), de novo onset of cGVHD (n = 19)) were analyzed in the absence of active GVHD by flow cytometry and enzyme-linked immunosorbent assay. All mean absolute cell counts are presented as cells per microliter; relative cell counts are presented as percentage of lymphocytes. Pts with subsequent de novo cGVHD had significantly higher relative and absolute counts of CD4+ T cells including higher absolute counts of CD4+ memory T cells (22.36%; 206.55/µl; 136/µl, respectively) compared to pts with subsequent quiescent onset of cGVHD (12.41%; 83.42/µl; 54.3/µl) and pts without cGVHD (10.55%) with regard to relative counts of CD4+ T cells. Similarly, significantly more relative and absolute regulatory T cell numbers (CD4+FOXP3+) were detected in pts with de novo onset of cGVHD (3.08% and 24.63/µl) compared to those in pts without (1.25% and 9.06/µl) or with quiescent onset of cGVHD (1.15% and 6.91/µl). Finally, relative B cell counts, including naïve and memory B cells, were also significantly decreased in pts developing quiescent cGVHD (0.85, 0.73, 0.12% resp.) when compared to pts with de novo onset (5.61, 5.24, 0.38%). The results demonstrate that alterations in immune reconstitution are already present before onset of clinical symptoms and differ between de novo and quiescent onset of disease.
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Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/inmunología , Trasplante de Células Madre Hematopoyéticas/tendencias , Adolescente , Adulto , Linfocitos B/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Citocinas/sangre , Citocinas/inmunología , Femenino , Enfermedad Injerto contra Huésped/sangre , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/tendencias , Adulto JovenRESUMEN
PURPOSE: A. fumigatus infections represent a major threat for patients with a suppressed immune system. Early diagnosis is of importance for a favorable outcome but appears to be difficult due to limited diagnostic procedures. Here we investigated the sensitivity of high-resolution ultrasound (HRU) for the detection of A. fumigatus infection in the liver. MATERIALS AND METHODS: BALB/c mice were intravenously infected with A. fumigatus and monitored by HRU, Doppler sonography (CCDS), contrast-enhanced ultrasound (CEUS), and real-time strain color-coded elastography (CCE) using a multi-frequency probe (6â-â15âMHz). Contrast media bolus injection of sulfur-hexafluoride micro-bubbles was applied and digital cine-loops from the arterial phase, as well as the portal venous phase up to the late phase of the whole liver were analyzed. All data were correlated to the histopathological findings. RESULTS: Using HRU and CEUS, a sonic shadow was detected in all infected animals. All Aspergillus-infected nodes from 3â-â6âmm in the liver showed a shadow with rim enhancement and no intranodal enhancement when using CEUS.âA. fumigatus infection was confirmed by CFU assessment and histopathological analysis. Granulomas were not associated with shadowing on B-mode. In contrast, granulomas with a diameter above 5âmm and a higher stiffness in CCE generated particularly an arterial rim enhancement and portal venous washout without contrast media uptake in the late phase. In addition, CEUS was able to define dynamic capillary microvascularization of infected liver areas. CONCLUSION: Liver lesions associated with A. fumigatus infection can be detected in mice when combined with CEUS and CCE in vivo.
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Aspergilosis/diagnóstico por imagen , Aspergillus fumigatus , Medios de Contraste , Gases , Aumento de la Imagen , Hepatopatías/diagnóstico por imagen , Animales , Aspergilosis/patología , Diagnóstico por Imagen de Elasticidad , Hígado/diagnóstico por imagen , Hígado/patología , Hepatopatías/patología , Ratones , Valores de ReferenciaRESUMEN
Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.
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Hepatitis C Crónica/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antivirales/uso terapéutico , Niño , Preescolar , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Salud Global , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/cirugía , Humanos , Lactante , Recién Nacido , Trasplante de Hígado/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Prevalencia , Adulto JovenRESUMEN
The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.
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Antivirales/uso terapéutico , Costo de Enfermedad , Hepatitis C Crónica/tratamiento farmacológico , Tamizaje Masivo , Modelos Biológicos , Progresión de la Enfermedad , Salud Global , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/epidemiología , Humanos , Prevalencia , Resultado del TratamientoRESUMEN
Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.
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Antivirales/uso terapéutico , Costo de Enfermedad , Hepatitis C Crónica/epidemiología , Modelos Biológicos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Salud Global , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Prevalencia , Adulto JovenRESUMEN
Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder. Genetic loci have not yet been identified by genome-wide association studies. Rare copy number variations (CNVs), such as chromosomal deletions or duplications, have been implicated in ADHD and other neurodevelopmental disorders. To identify rare (frequency ≤1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8 × 10(-4) after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6: 162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2 × 10(-3) after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3 × 10(-2)). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.
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Trastorno por Déficit de Atención con Hiperactividad/genética , Variaciones en el Número de Copia de ADN/genética , Predisposición Genética a la Enfermedad , Ubiquitina-Proteína Ligasas/genética , Adolescente , Adulto , Anciano , Niño , Planificación en Salud Comunitaria , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Metastatic melanoma is a malignancy with one of the highest mortality rates. However, with the introduction of new drugs during the last decade, the prognosis of patients began to improve. Ipilimumab is one of the first so âcalled modern drugs in melanoma treatment. The therapy is often complicated by adverse effects which are referred as immunerelated adverse events due to its mechanism of action. CASE: We present a case of 68-year-âold women with metastatic melanoma who underwent treatment with ipilimumab. The patient encountered several adverse events during the treatment. Some of them are quite common (e.g. skin affections), others (e.g. endocrinopathies) are less frequent. CONCLUSION: This case study highlights the need for close observation not only during the actual treatment with ipilimumab, but also several weeks or months after the last dose. This case study also demonstrates further need of education of doctors who do not usually come in to contact with such patients.
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Anticuerpos Monoclonales/efectos adversos , Antineoplásicos/efectos adversos , Melanoma/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Femenino , Humanos , IpilimumabRESUMEN
EG-VEGF is an angiogenic factor that we identified as a new placental growth factor during human pregnancy. EG-VEGF is also expressed in the mouse fetal membrane (FM) by the end of gestation, suggesting a local role for this protein in the mechanism of parturition. However, injection of EG-VEGF to gravid mice did not induce labor, suggesting a different role for EG-VEGF in parturition. Here, we searched for its role in the FM in relation to human parturition. Human pregnant sera and total FM, chorion, and amnion were collected during the second and third trimesters from preterm no labor, term no labor, and term labor patients. Primary human chorion trophoblast and FM explants cultures were also used. We demonstrate that circulating EG-VEGF increased toward term and significantly decreased at the time of labor. EG-VEGF production was higher in the FM compared to placentas matched for gestational age. Within the FM, the chorion was the main source of EG-VEGF. EG-VEGF receptors, PROKR1 and PROKR2, were differentially expressed within the FM with increased expression toward term and an abrupt decrease with the onset of labor. In chorion trophoblast and FM explants collected from nonlaboring patients, EG-VEGF decreased metalloproteinase-2 and -9 activities and increased PGDH (prostaglandin-metabolizing enzyme) expression. Altogether these data demonstrate that EG-VEGF is a new cytokine that acts locally to ensure FM protection in late pregnancy. Its fine contribution to the initiation of human labor is exhibited by the abrupt decrease in its levels as well as a reduction in its receptors.
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Corion/metabolismo , Regulación hacia Abajo , Trabajo de Parto/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto , Amnios/metabolismo , Células Cultivadas , Cesárea , Corion/citología , Femenino , Humanos , Trabajo de Parto/sangre , Placenta/metabolismo , Placentación , Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Péptidos/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Técnicas de Cultivo de Tejidos , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
Identifiable causes of fetal growth restriction (FGR) account for 30 % of cases, but the remainders are idiopathic and are frequently associated with placental dysfunction. We have shown that the angiogenic factor endocrine gland-derived VEGF (EG-VEGF) and its receptors, prokineticin receptor 1 (PROKR1) and 2, (1) are abundantly expressed in human placenta, (2) are up-regulated by hypoxia, (3) control trophoblast invasion, and that EG-VEGF circulating levels are the highest during the first trimester of pregnancy, the period of important placental growth. These findings suggest that EG-VEGF/PROKR1 and 2 might be involved in normal and FGR placental development. To test this hypothesis, we used placental explants, primary trophoblast cultures, and placental and serum samples collected from FGR and age-matched control women. Our results show that (1) EG-VEGF increases trophoblast proliferation ([(3)H]-thymidine incorporation and Ki67-staining) via the homeobox-gene, HLX (2) the proliferative effect involves PROKR1 but not PROKR2, (3) EG-VEGF does not affect syncytium formation (measurement of syncytin 1 and 2 and ß hCG production) (4) EG-VEGF increases the vascularization of the placental villi and insures their survival, (5) EG-VEGF, PROKR1, and PROKR2 mRNA and protein levels are significantly elevated in FGR placentas, and (6) EG-VEGF circulating levels are significantly higher in FGR patients. Altogether, our results identify EG-VEGF as a new placental growth factor acting during the first trimester of pregnancy, established its mechanism of action, and provide evidence for its deregulation in FGR. We propose that EG-VEGF/PROKR1 and 2 increases occur in FGR as a compensatory mechanism to insure proper pregnancy progress.
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Retardo del Crecimiento Fetal/metabolismo , Placenta/metabolismo , Factor de Crecimiento Endotelial Vascular Derivado de Glándula Endocrina/metabolismo , Hipoxia de la Célula , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Femenino , Retardo del Crecimiento Fetal/patología , Células Gigantes/citología , Proteínas de Homeodominio/metabolismo , Humanos , Placenta/citología , Placentación , Embarazo , Primer Trimestre del Embarazo , ARN Mensajero/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Péptidos/genética , Receptores de Péptidos/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Factores de Transcripción/metabolismo , Trofoblastos/citología , Trofoblastos/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Factor de Crecimiento Endotelial Vascular Derivado de Glándula Endocrina/genéticaRESUMEN
AIM: The present report summarizes rodent studies with vildagliptin, relevant to predicting pancreatitis or pancreatic cancer in man. METHODS: As part of the regulatory development program for vildagliptin, a rodent toxicity program included two 104-week rodent (mouse and rat) carcinogenicity studies that were conducted according to guidelines assigned in Food and Drug Administration's Draft Guidance for Industry. RESULTS: Vildagliptin exposure in animals was evaluated for its effects on endocrine and exocrine pancreas. Two-year carcinogenicity studies were conducted in rats at oral doses up to 900 mg/kg (approximately 200 times the human exposure at the maximum recommended dose) and in mice at oral doses up to 1000 mg/kg (up to 240 times the human exposure at the maximum recommended dose). The results from these studies show the expected preservation and growth of the endocrine ß-cells with no significant findings in the exocrine acinar pancreas. There was no evidence of inflammatory infiltrates characteristic of pancreatitis, no palpable mass detection based on gross examination or any microscopic findings indicative of pancreatic islet cell (endocrine), acinar cell (exocrine) or ductal (exocrine) neoplasia in rat or mouse. CONCLUSIONS: Evaluation of vildagliptin in 2-year preclinical carcinogenicity studies in both rats and mice indicates that while vildagliptin results in pharmacological benefits to the endocrine pancreas, this was not associated with any evidence of pancreatitis, pancreatic islet cell, acinar cell or ductal neoplasia. These data predict no increased risk of pancreatic cancer in man.
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Adamantano/análogos & derivados , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Islotes Pancreáticos/efectos de los fármacos , Nitrilos/efectos adversos , Páncreas Exocrino/efectos de los fármacos , Neoplasias Pancreáticas/inducido químicamente , Pancreatitis/inducido químicamente , Pirrolidinas/efectos adversos , Adamantano/efectos adversos , Animales , Femenino , Humanos , Islotes Pancreáticos/patología , Masculino , Ratones , Ratones Transgénicos , Páncreas Exocrino/patología , Neoplasias Pancreáticas/patología , Pancreatitis/patología , Valor Predictivo de las Pruebas , Ratas , Ratas Transgénicas , Ratas Wistar , VildagliptinaRESUMEN
Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor reported to be specific for endocrine tissues, including the placenta. Its biological activity is mediated via two G protein-coupled receptors, prokineticin receptor 1 (PROKR1) and prokineticin receptor 2 (PROKR2). We have recently shown that (i) EG-VEGF expression peaks between the 8th and 11th weeks of gestation, (ii) its mRNA and protein levels are up-regulated by hypoxia, (iii) EG-VEGF is a negative regulator of trophoblast invasion and (iv) its circulating levels are increased in preeclampsia (PE), the most threatening pathology of pregnancy. Here, we investigated the regulation of the expression of EG-VEGF and its receptors by hCG, a key pregnancy hormone that is also deregulated in PE. During the first trimester of pregnancy, hCG and EG-VEGF exhibit the same pattern of expression, suggesting that EG-VEGF is potentially regulated by hCG. Both placental explants (PEX) and primary cultures of trophoblasts from the first trimester of pregnancy were used to investigate this hypothesis. Our results show that (i) LHCGR, the hCG receptor, is expressed both in cyto- and syncytiotrophoblasts, (ii) hCG increases EG-VEGF, PROKR1 and PROKR2 mRNA and protein expression in a dose- and time-dependent manner, (iii) hCG increases the release of EG-VEGF from PEX conditioned media, (iv) hCG effects are transcriptional and post-transcriptional and (v) the hCG effects are mediated by cAMP via cAMP response elements present in the EG-VEGF promoter region. Altogether, these results demonstrate a new role for hCG in the regulation of EG-VEGF and its receptors, an emerging regulatory system in placental development.
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Gonadotropina Coriónica/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Péptidos/metabolismo , Factor de Crecimiento Endotelial Vascular Derivado de Glándula Endocrina/metabolismo , Secuencia de Bases , Células Cultivadas , Gonadotropina Coriónica/farmacología , Cartilla de ADN/genética , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Técnicas In Vitro , Modelos Biológicos , Datos de Secuencia Molecular , Placenta/efectos de los fármacos , Placenta/metabolismo , Placentación , Embarazo , Primer Trimestre del Embarazo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores de HL/metabolismo , Receptores de Péptidos/genética , Trofoblastos/efectos de los fármacos , Trofoblastos/metabolismo , Factor de Crecimiento Endotelial Vascular Derivado de Glándula Endocrina/genéticaRESUMEN
BACKGROUND: Intensity-modulated radiation therapy (IMRT) is the method of choice in external-beam radiotherapy tolocalized prostate cancer. This work analyses five year results of IMRT with a dose of 78/82 Gy. PATIENTS AND METHODS: From June 2003 to December 2007, the IMRT technique was employed to treat 233 patients with T1-3 N0 M0 prostate cancer. It was supplemented by hormone therapy especially in high-risk patients. Two IMRT techniques were applied - IMRT with a dose of 78 Gy in 39 fractions to prostate and seminal vesicles (SV) (IMRT 78) and IMRT with simultaneous integrated 82 Gy boost to prostate concurrently with 73,8 Gy in 41 fractions to SV (IMRT SIB 82). The IMRT 78 technique was used in 160 patients (69%). Seventy-three (31%) patients with intermediate (IR) or high-risk (HR) prostate cancer without SV involvement were treated with IMRT SIB 82 technique. The PSA relapse was defined as an increase in PSA of at least 2.0 ng/mL above the nadir or in comparison to the value at the initiation of hormone therapy. Clinical relapse was defined as an occurence of distant metastases and/or local recurrence. RESULTS: The median follow-up of our patients´ population was 4.3 years (range 0.6-8.9 years). The estimated 5-year PSA relapse-free survival in low-risk (LR), IR and HR patients was 86%, 89% and 83%, respectively (p = NS). In a multivariate analysis, Gleason score (GS) 8-10 was associated with significantly higher risk of PSA relapse (RR 2.76), while higher age at the time of diagnosis significantly decreased the PSA relapse risk (RR 0.94). The estimated 5-year clinical relapse-free survival in LR, IR and HR patients was 100%, 99% and 95%, respectively (p = NS). In a univariate analysis, both GS and PSA had a significant impact on the 5-year clinical relapse-free survival - GS 2-7 97 % vs GS 8-10 88 % (p = 0.03), PSA 20 98 % vs PSA > 20 85 % (p < 0.01). CONCLUSION: Treatment of localized prostate cancer using IMRT with a dose 78/82 Gy yielded an excellent 5-year tumour control with a risk of clinical relapse being less than 5%.
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Neoplasias de la Próstata/radioterapia , Radioterapia de Intensidad Modulada/métodos , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/mortalidad , Dosis de Radiación , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/efectos adversos , Resultado del TratamientoRESUMEN
Annual fish live exclusively in temporary wetlands and are among the shortest-lived vertebrates in the world. These fish persist in these habitats due to drought-resistant eggs, that which, through diapauses are able to detect stimuli from the environment to start the development processes. They are also able to direct their embryonic development in different trajectories with different development times. Our objective in this paper was to describe the different stages of embryonic development of Austrolebias wolterstorffi, a critically endangered annual fish. A total of 27 stages of embryonic development were identified for the two observed developmental pathways (direct and diapause 2). Of these 27 developmental stages observed, 24 were identical between the two types of trajectories and three different. A total of 90% of the embryos that completed their development proceeded normally, without pauses. One embryo had a different development from the others, entering diapause 2, with a pause in development for 48 h. Although the embryonic development of A. wolterstorffi is similar to that of other Neotropical annual fish species, the diapause 2 occurs when the embryo has a large body size and a well-developed brain, indicating that the lack of embryonic information of the genus Austrolebias may hide characteristics still undescribed or even different survival strategies than what has been observed for other annual fish.
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Ciprinodontiformes , Diapausa , Animales , Desarrollo EmbrionarioRESUMEN
Dyslexia is one of the most common learning disorders affecting about 5% of all school-aged children. It has been shown that event-related potential measurements reveal differences between dyslexic children and age-matched controls. This holds particularly true for mismatch negativity (MMN), which reflects automatic speech deviance processing and is altered in dyslexic children. We performed a whole-genome association analysis in 200 dyslexic children, focusing on MMN measurements. We identified rs4234898, a marker located on chromosome 4q32.1, to be significantly associated with the late MMN component. This association could be replicated in an independent second sample of 186 dyslexic children, reaching genome-wide significance in the combined sample (P = 5.14e-08). We also found an association between the late MMN component and a two-marker haplotype of rs4234898 and rs11100040, one of its neighboring single nucleotide polymorphisms (SNPs). In the combined sample, this marker combination withstands correction for multiple testing (P = 6.71e-08). Both SNPs lie in a region devoid of any protein-coding genes; however, they both show significant association with mRNA-expression levels of SLC2A3 on chromosome 12, the predominant facilitative glucose transporter in neurons. Our results suggest a possible trans-regulation effect on SLC2A3, which might lead to glucose deficits in dyslexic children and could explain their attenuated MMN in passive listening tasks.
Asunto(s)
Cromosomas Humanos Par 4 , Dislexia/genética , Potenciales Evocados Auditivos/genética , Transportador de Glucosa de Tipo 3/genética , Percepción del Habla/genética , Adolescente , Estudios de Casos y Controles , Niño , Variación Contingente Negativa/genética , Discriminación en Psicología/fisiología , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Masculino , Valores de Referencia , Adulto JovenRESUMEN
Layered samples Si(100)/C/Ni/BC(x)N(y) and Si(100)/C/Cu/BC(x)N(y) were produced by physical vapor deposition of a metal (Ni, Cu, resp.) and low-pressure chemical vapor deposition of the boron carbonitride on a Si(100) substrate. Between the Si and the Ni (Cu) and on the surface of the Ni (Cu) layer, thin carbon layers were deposited, as a diffusion barrier or as a protection against oxidation, respectively. Afterwards, the surface carbon layer was removed. As precursor, trimethylamine borane and, as an auxiliary gas, H(2) and NH(3) were used, respectively. The chemical compositions of the layers and of the interfaces in between were characterized by total-reflection X-ray fluorescence spectrometry combined with near-edge X-ray absorption fine-structure spectroscopy, X-ray photoelectron spectroscopy, and secondary ion mass spectrometry. The application of H(2) yielded the BC(x)N(y) compound whereas the use of NH(3) led to a mixture of h-BN and graphitic carbon. At the BC(x)N(y)/metal interface, metal borides could be identified. At the relatively high synthesis temperature of 700 °C, broad regions of Cu or Ni and Si were observed between the metal layer and the substrate Si.
RESUMEN
Transition metal phthalocyanines (MPc's) are an interesting class of material, and their magnetic and electronic properties are determined by the orbital occupation of the transition metal 3d orbitals incorporated in the molecules center. Thus, the ground state configuration of the transition metal center is very important for a complete understanding of these materials. We present experimental data taken using x-ray absorption and x-ray photoemission spectroscopy together with a theoretical interpretation of MPc series with M=Zn, Cu, Ni, Co, Fe, and Mn. The combination of these methods allows us to narrow down possible dominating ground state configurations and shed a brighter light on the electronic structure of these complexes.
RESUMEN
Buschke Lownestein's tumour is a giant acuminate condyloma characterised by its degenerative potential, its invasive nature and its recurrence after treatment. It is a rare condition, transmitted mainly by sexual transmission and induced by to the human papillomavirus (HPV). The discussion will be illustrated by a clinical case The treatment is still under discussion but surgery seems to be the best option. Management during pregnancy is more complex since it must take into account the mother and her fetus. The delivery route is still debated. The post-treatment evolution was satisfactory and without recurrence until the delivery which, due to the antecedent of 3 caesarean sections, was carried out by cesarean section. HPV vaccination, sex education and early treatment of condyloma lesions should prevent and in any case improve the prognosis of this disease.
Asunto(s)
Tumor de Buschke-Lowenstein , Condiloma Acuminado , Tumor de Buschke-Lowenstein/patología , Tumor de Buschke-Lowenstein/cirugía , Cesárea , Condiloma Acuminado/patología , Condiloma Acuminado/cirugía , Femenino , Humanos , Papillomaviridae , EmbarazoRESUMEN
OBJECTIVE: To analyse the introduction of the Couder manoeuvre in our level 3 maternity unit shortly after its introduction in 2019. Then, to evaluate and compare the rate of perineal injuries between 2017, when the manoeuvre was not performed at all, and 2020. MATERIALS AND METHOD: A single-centre retrospective study of patients who delivered a singleton eutociously at term from 1 January to 31 December 2017 and 2020. RESULTS: In total, 2930 records were analysed. The Couder manoeuvre rate was 32.12% in 2020. A change in the distribution of perineal lesions was observed: the rate of intact perineum increased (P<0.001), while 2nd degree lesions decreased between 2017 and 2020 (P<0.05). The 1st degree perineum and obstetric anal sphincter injuries remained stable. The rate of episiotomy decreased significantly by almost a factor of 7. CONCLUSION: The practice of the Couder manoeuvre can be implemented fairly quickly after training of the actors with nearly a third of normal deliveries at term concerned one year after its introduction. This manoeuvre seems, in our practice, to have contributed to the reduction, as previously reported, of the rate of second degree perineal injuries.