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All non-Mimosoid nodulated genera in the legume subfamily Caesalpinioideae confine their rhizobial symbionts within cell wall-bound 'fixation threads' (FTs). The exception is the large genus Chamaecrista in which shrubs and subshrubs house their rhizobial bacteroids more intimately within symbiosomes, whereas large trees have FTs. This study aimed to unravel the evolutionary relationships between Chamaecrista growth habit, habitat, nodule bacteroid type, and rhizobial genotype. The growth habit, bacteroid anatomy, and rhizobial symbionts of 30 nodulated Chamaecrista species native to different biomes in the Brazilian state of Bahia, a major centre of diversity for the genus, was plotted onto an ITS-trnL-F-derived phylogeny of Chamaecrista. The bacteroids from most of the Chamaecrista species examined were enclosed in symbiosomes (SYM-type nodules), but those in arborescent species in the section Apoucouita, at the base of the genus, were enclosed in cell wall material containing homogalacturonan (HG) and cellulose (FT-type nodules). Most symbionts were Bradyrhizobium genotypes grouped according to the growth habits of their hosts, but the tree, C. eitenorum, was nodulated by Paraburkholderia. Chamaecrista has a range of growth habits that allow it to occupy several different biomes and to co-evolve with a wide range of (mainly) bradyrhizobial symbionts. FTs represent a less intimate symbiosis linked with nodulation losses, so the evolution of SYM-type nodules by most Chamaecrista species may have (i) aided the genus-wide retention of nodulation, and (ii) assisted in its rapid speciation and radiation out of the rainforest into more diverse and challenging habitats.
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Chamaecrista , Filogenia , Bosque Lluvioso , Simbiosis , Chamaecrista/fisiología , Chamaecrista/genética , Chamaecrista/crecimiento & desarrollo , Brasil , Ecosistema , Rhizobium/fisiología , Nodulación de la Raíz de la Planta/fisiología , Evolución Biológica , Fijación del NitrógenoRESUMEN
BACKGROUND: In men with a detectable prostate-specific antigen (PSA) level after prostatectomy for prostate cancer, salvage prostate bed radiotherapy (PBRT) results in about 70% of patients being free of progression at 5 years. A three-group randomised trial was designed to determine whether incremental gains in patient outcomes can be achieved by adding either 4-6 months of short-term androgen deprivation therapy (ADT) to PBRT, or both short-term ADT and pelvic lymph node radiotherapy (PLNRT) to PBRT. METHODS: The international, multicentre, randomised, controlled SPPORT trial was done at 283 radiation oncology cancer treatment centres in the USA, Canada, and Israel. Eligible patients (aged ≥18 years) were those who after prostatectomy for adenocarcinoma of the prostate had a persistently detectable or an initially undetectable and rising PSA of between 0·1 and 2·0 ng/mL. Patients with and without lymphadenectomy (N0/Nx) were eligible if there was no clinical or pathological evidence of lymph node involvement. Other eligibility criteria included pT2 or pT3 disease, prostatectomy Gleason score of 9 or less, and a Zubrod performance status of 0-1. Eligible patients were randomly assigned to receive PBRT alone at a dose of 64·8-70·2 Gy at 1·8 Gy per fraction daily (group 1), PBRT plus short-term ADT (group 2), or PLNRT (45 Gy at 1·8 Gy per fraction, and then a volume reduction made to the planning target volume for the remaining 19·8-25 ·2 Gy) plus PBRT plus short-term ADT (group 3). The primary endpoint was freedom from progression, in which progression was defined as biochemical failure according to the Phoenix definition (PSA ≥2 ng/mL over the nadir PSA), clinical failure (local, regional, or distant), or death from any cause. A planned interim analysis of 1191 patents with minimum potential follow-up time of 5 years applied a Haybittle-Peto boundary of p<0·001 (one sided) for comparison of 5-year freedom from progression rates between the treatment groups. This trial is registered with ClinicalTrials.gov, NCT00567580. The primary objectives of the trial have been completed, although long-term follow-up is continuing. FINDINGS: Between March 31, 2008, and March 30, 2015, 1792 eligible patients were enrolled and randomly assigned to the three treatment groups (592 to group 1 [PBRT alone], 602 to group 2 [PBRT plus short-term ADT], and 598 to group 3 [PLNRT plus PBRT plus short-term ADT]). 76 patients subsequently found to be ineligible were excluded from the analyses; thus, the evaluable patient population comprised 1716 patients. At the interim analysis (n=1191 patients; data cutoff May 23, 2018), the Haybittle-Peto boundary for 5-year freedom from progression was exceeded when group 1 was compared with group 3 (difference 17·9%, SE 2·9%; p<0·0001). The difference between groups 2 and 3 did not exceed the boundary (p=0·0063). With additional follow-up beyond the interim analysis (the final planned analysis; data cutoff May 26, 2021), at a median follow-up among survivors of 8·2 years (IQR 6·6-9·4), the 5-year freedom from progression rates in all 1716 eligible patients were 70·9% (95% CI 67·0-74·9) in group 1, 81·3% (78·0-84·6) in group 2, and 87·4% (84·7-90·2) in group 3. Per protocol criteria, freedom from progression in group 3 was superior to groups 1 and 2. Acute (≤3 months after radiotherapy) grade 2 or worse adverse events were significantly more common in group 3 (246 [44%] of 563 patients) than in group 2 (201 [36%] of 563; p=0·0034), which, in turn, were more common than in group 1 (98 [18%] of 547; p<0·0001). Similar findings were observed for grade 3 or worse adverse events. However, late toxicity (>3 months after radiotherapy) did not differ significantly between the groups, apart from more late grade 2 or worse blood or bone marrow events in group 3 versus group 2 (one-sided p=0·0060) attributable to the addition of PLNRT in this group. INTERPRETATION: The results of this randomised trial establish the benefit of adding short-term ADT to PBRT to prevent progression in prostate cancer. To our knowledge, these are the first such findings to show that extending salvage radiotherapy to treat the pelvic lymph nodes when combined with short-term ADT results in meaningful reductions in progression after prostatectomy in patients with prostate cancer. FUNDING: National Cancer Institute.
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Neoplasias de la Próstata , Oncología por Radiación , Adolescente , Adulto , Antagonistas de Andrógenos/uso terapéutico , Andrógenos , Humanos , Ganglios Linfáticos/patología , Masculino , Próstata/patología , Antígeno Prostático Específico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/radioterapia , Terapia Recuperativa/efectos adversosRESUMEN
PURPOSE: To evaluate the risk of sarcopenia on the length of hospital stay and deaths in preoperative cancer patients as well its relation to physical and functional capacity. METHODS: Preoperative patients admitted to the Cancer Hospital of Mato Grosso comprised the sample. Sociodemographic data, lifestyle data, and a questionnaire for sarcopenia screening were collected. Subsequently, total body mass, height, muscle strength, muscle mass, and physical performance were evaluated. The primary, secondary and tertiary outcomes were sarcopenia, length of stay and death, respectively. The data were tabulated and analyzed using the statistical software SPSS (25.0). The significance level was 5%. RESULTS: We observed 12 (7.4%) patients with low muscle strength, 20 (12.3%) patients with low muscle mass, 11 (6.8%) patients with low physical performance, and 18 (11.1%) patients with scores for possible sarcopenia. When the risk of sarcopenia was observed, 44 (27.2%) patients had at least one risk related to muscle disorder. When analyzing the prevalence and association of sarcopenia with sociodemographic variables, we observed that education level was associated with sarcopenia (p = 0.031). In addition, there was an association between preoperative sarcopenia and postoperative death (p = 0.006). Finally, there were important correlations between muscle strength and physical performance (p < 0.05), between muscle strength and the sarcopenia questionnaire (p < 0.001), and between physical performance and the sarcopenia questionnaire (p < 0.05). CONCLUSION: The results suggest the need for counseling and the need to evaluate patients for risk of sarcopenia, since early intervention, such as dietary supplementation and physical exercise, may favor a better postoperative prognosis, possibly corresponding to shorter hospital stays and longer survival and quality of life for patients, especially those who will undergo surgical procedures.
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Sarcopenia , Humanos , Sarcopenia/etiología , Sarcopenia/complicaciones , Calidad de Vida , Fuerza Muscular/fisiología , Pronóstico , Estilo de Vida , Músculo Esquelético/fisiologíaRESUMEN
The growing use of multimodal high-resolution volumetric data in pre-clinical studies leads to challenges related to the management and handling of the large amount of these datasets. Contrarily to the clinical context, currently there are no standard guidelines to regulate the use of image compression in pre-clinical contexts as a potential alleviation of this problem. In this work, the authors study the application of lossy image coding to compress high-resolution volumetric biomedical data. The impact of compression on the metrics and interpretation of volumetric data was quantified for a correlated multimodal imaging study to characterize murine tumor vasculature, using volumetric high-resolution episcopic microscopy (HREM), micro-computed tomography (µCT), and micro-magnetic resonance imaging (µMRI). The effects of compression were assessed by measuring task-specific performances of several biomedical experts who interpreted and labeled multiple data volumes compressed at different degrees. We defined trade-offs between data volume reduction and preservation of visual information, which ensured the preservation of relevant vasculature morphology at maximum compression efficiency across scales. Using the Jaccard Index (JI) and the average Hausdorff Distance (HD) after vasculature segmentation, we could demonstrate that, in this study, compression that yields to a 256-fold reduction of the data size allowed to keep the error induced by compression below the inter-observer variability, with minimal impact on the assessment of the tumor vasculature across scales.
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Compresión de Datos , Neoplasias , Humanos , Animales , Ratones , Compresión de Datos/métodos , Microtomografía por Rayos X , Imagen por Resonancia Magnética , Imagen Multimodal , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Nitrogen-fixing symbiosis is globally important in ecosystem functioning and agriculture, yet the evolutionary history of nodulation remains the focus of considerable debate. Recent evidence suggesting a single origin of nodulation followed by massive parallel evolutionary losses raises questions about why a few lineages in the N2 -fixing clade retained nodulation and diversified as stable nodulators, while most did not. Within legumes, nodulation is restricted to the two most diverse subfamilies, Papilionoideae and Caesalpinioideae, which show stable retention of nodulation across their core clades. We characterize two nodule anatomy types across 128 species in 56 of the 152 genera of the legume subfamily Caesalpinioideae: fixation thread nodules (FTs), where nitrogen-fixing bacteroids are retained within the apoplast in modified infection threads, and symbiosomes, where rhizobia are symplastically internalized in the host cell cytoplasm within membrane-bound symbiosomes (SYMs). Using a robust phylogenomic tree based on 997 genes from 147 Caesalpinioideae genera, we show that losses of nodulation are more prevalent in lineages with FTs than those with SYMs. We propose that evolution of the symbiosome allows for a more intimate and enduring symbiosis through tighter compartmentalization of their rhizobial microsymbionts, resulting in greater evolutionary stability of nodulation across this species-rich pantropical legume clade.
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Fabaceae , Rhizobium , Ecosistema , Fabaceae/genética , Nitrógeno , Fijación del Nitrógeno , Nodulación de la Raíz de la Planta/genética , Nódulos de las Raíces de las Plantas , SimbiosisRESUMEN
Atmospheric radiocarbon (14C) recorded in tree rings has been widely used for atmospheric 14C calibration purposes and climate studies. But atmospheric 14C records have been limited along tropical latitudes. Here we report a sequence from 1938 to 2007 of precisely measured 14C dates in tree rings of the parenchyma-rich Hymenolobium petraeum tree species (Porto Trombetas, 1°S, 56°W) from the Central Brazilian Amazon. H. petraeum has discernible growth ring boundaries that allow dating techniques to be employed to produce calendrical dates. Bomb-peak tree-ring 14C reconstruction coincides with the broader changes associated with reported values of the Southern Hemisphere atmospheric 14C curve (SH zone 3; values within the ±2σ interval), suggesting that inter-hemispheric air-mass transport of excess-14C injected into the stratosphere during intensive atmospheric nuclear tests is relatively uniform across distinct longitudinal regions. From the early 1980s onwards, H. petraeum had lower 14C values than other pantropical 14C records. Through 14C-based estimation, we found a strong influence of fossil-fuel CO2 contributions from Porto Trombetas mining operations and shipping traffic on inland waterways. An increase of at least 6.3 ± 0.8 ppm of fossil-fuel CO2 has been detected by 14C. Our findings invite further 14C analyses using tree rings of tropical tree species as a potential tracer for a wide range of environmental sources of atmospheric 14C-variability.
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Bombas (Dispositivos Explosivos) , Combustibles Fósiles , Dióxido de Carbono/análisis , Clima , MineríaRESUMEN
With the advancement of the Covid-19 pandemic, this work aims to find molecules that can inhibit the attraction between the Spike proteins of the SARS-COV-2 virus and human ACE2. The results of molecular docking positioned four molecules at the interaction site Tyr-491(Spike)-Glu-37(ACE2) and one at the site Gly-488(Spike)-Lys-353(ACE2). The QTAIM and IQA data showed that the 1629 molecule had a significant inhibitory effect on the Gly488-Ly353 site, decreasing the Laplacian of the electronic density of the BCP O4-N10. The molecule 2542 showed an inhibitory effect in two regions of interaction of the Tyr491-Glu37 site, acting on the BCPs H30-H33 and O8-H31 while the ligand 2600, in conformation 26, presented a similar effect only on the BCP O8-H31 of that same interactive site. Thus, the data suggest laboratory tests of a combination of molecules that can act at two sites of interaction simultaneously, using the combination of 1629/2542 and 1629/2600 ligands.
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Intelligent approaches in sports using IoT devices to gather data, attempting to optimize athlete's training and performance, are cutting edge research. Synergies between recent wearable hardware and wireless communication strategies, together with the advances in intelligent algorithms, which are able to perform online pattern recognition and classification with seamless results, are at the front line of high-performance sports coaching. In this work, an intelligent data analytics system for swimmer performance is proposed. The system includes (i) pre-processing of raw signals; (ii) feature representation of wearable sensors and biosensors; (iii) online recognition of the swimming style and turns; and (iv) post-analysis of the performance for coaching decision support, including stroke counting and average speed. The system is supported by wearable inertial (AHRS) and biosensors (heart rate and pulse oximetry) placed on a swimmer's body. Radio-frequency links are employed to communicate with the heart rate sensor and the station in the vicinity of the swimming pool, where analytics is carried out. Experiments were carried out in a real training setup, including 10 athletes aged 15 to 17 years. This scenario resulted in a set of circa 8000 samples. The experimental results show that the proposed system for intelligent swimming analytics with wearable sensors effectively yields immediate feedback to coaches and swimmers based on real-time data analysis. The best result was achieved with a Random Forest classifier with a macro-averaged F1 of 95.02%. The benefit of the proposed framework was demonstrated by effectively supporting coaches while monitoring the training of several swimmers.
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Rendimiento Atlético , Técnicas Biosensibles , Dispositivos Electrónicos Vestibles , Atletas , Humanos , NataciónRESUMEN
The authors of the above-mentioned published article inadvertently omitted Dirk Redecker, Dioumacor Fall and Diaminatou Sanogo from the list of authors. The names and their affiliations presented in this paper.
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Arbuscular mycorrhizal fungi (AMF) absorb and translocate nutrients from soil to their host plants by means of a wide network of extraradical mycelium (ERM). Here, we assessed whether nitrogen-fixing rhizobia can be transferred to the host legume Glycine max by ERM produced by Glomus formosanum isolate CNPAB020 colonizing the grass Urochloa decumbens. An H-bridge experimental system was developed to evaluate the migration of ERM and of the GFP-tagged Bradyrhizobium diazoefficiens USDA 110 strain across an air gap compartment. Mycorrhizal colonization, nodule formation in legumes, and occurrence of the GFP-tagged strain in root nodules were assessed by optical and confocal laser scanning microscopy. In the presence of non-mycorrhizal U. decumbens, legume roots were neither AMF-colonized nor nodulated. In contrast, G. formosanum ERM crossing the discontinuous compartment connected mycorrhizal U. decumbens and G. max roots, which showed 30-42% mycorrhizal colonization and 7-11 nodules per plant. Fluorescent B. diazoefficiens cells were detected in 94% of G. max root nodules. Our findings reveal that, besides its main activity in nutrient transfer, ERM produced by AMF may facilitate bacterial translocation and the simultaneous associations of plants with beneficial fungi and bacteria, representing an important structure, functional to the establishment of symbiotic relationships.
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Fabaceae , Micorrizas , Bacterias , Nitrógeno , Raíces de Plantas , SimbiosisRESUMEN
The extraradical mycelium (ERM) produced by arbuscular mycorrhizal fungi is fundamental for the maintenance of biological fertility in agricultural soils, representing an important inoculum source, together with spores and mycorrhizal root fragments. Its viability and structural traits, such as density, extent and interconnectedness, which are positively correlated with the growth and nutrition of host plants, may be affected by different agronomic practices, including the use of pesticides and by different mycorrhizospheric communities. This work, carried out using a whole-plant experimental model system, showed that structural traits of ERM, such as length and density, were strongly decreased by the herbicides dicamba and glufosinolate and the fungicides benomyl and fenhexamid, while anastomosis frequency and hyphal branching were differentially modulated by singly inoculated mycorrhizospheric bacteria, depending on their identity.
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Fenómenos Fisiológicos Bacterianos , Cichorium intybus/microbiología , Fungicidas Industriales/farmacología , Glomeromycota/efectos de los fármacos , Glomeromycota/crecimiento & desarrollo , Herbicidas/farmacología , Micelio/crecimiento & desarrollo , Micorrizas/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Benomilo/farmacología , Cichorium intybus/crecimiento & desarrollo , Dicamba/farmacología , Hifa/efectos de los fármacos , Hifa/crecimiento & desarrollo , Micelio/efectos de los fármacos , Micorrizas/crecimiento & desarrollo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/microbiología , Esporas Bacterianas/genética , Esporas Bacterianas/aislamiento & purificación , Esporas Bacterianas/fisiologíaRESUMEN
Arbuscular mycorrhizal fungi (AMF) play a major role as biofertilizer for sustainable agriculture. Nevertheless, it is still poorly documented whether inoculated AMF can successfully establish in field soils as exotic AMF and improve plant growth and productivity. Further, the fate of an exogenous inoculum is still poorly understood. Here, we pre-inoculated two cultivars (Tasset and Gola) of the fruit tree Ziziphus mauritiana (jujube) with the exotic AM fungus Rhizophagus irregularis isolate IR27 before transplantation in the field. In two experiments, tracking and quantification of R. irregularis IR27 were assessed in a 13-month-old jujube and an 18-month-old jujube in two fields located in Senegal. Our results showed that the inoculant R. irregularis IR27 was quantitatively traced and discriminated from native R. irregularis isolates in roots by using a qPCR assay targeting a fragment of the RNA polymerase II gene (RPB1), and that the inoculum represented only fractions ranging from 11 to 15% of the Rhizophagus genus in the two plantations 13 and 18 months after transplantation, respectively. This study validates the use of the RPB1 gene as marker for a relative quantification of a mycorrhizal inoculant fungus isolate in the field.
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Glomeromycota/fisiología , Micorrizas/fisiología , Ziziphus/microbiología , Secuencia de Aminoácidos , Proteínas Fúngicas/análisis , ARN Polimerasa II/análisis , Senegal , Alineación de SecuenciaRESUMEN
Tripartite interactions between legumes and their root symbionts (rhizobia and arbuscular mycorrhizal fungi, AMF) are poorly understood, although it is well established that only specific combinations of symbionts lead to optimal plant growth. A classic example in which to investigate such interactions is the Brazilian legume tree Piptadenia gonoacantha (Caesalpinioideae), for which efficient nodulation has been described as dependent on the presence of AMF symbiosis. In this study, we compared the nodulation behaviour of several rhizobial strains with or without AMF inoculation, and performed analyses on nodulation, nodule cytology, N-fixing efficiency, and plant growth response. Nodulation of P. gonoacantha does not rely on the presence of AMF, but mycorrhization was rhizobial strain-dependent, and nodule effectiveness and plant growth were dependent on the presence of specific combinations of rhizobial strains and AMF. The co-occurrence of both symbionts within efficient nodules and the differentiation of bacteroids within nodule cells were also demonstrated. Novel close interactions and interdependency for the establishment and/or functioning of these symbioses were also revealed in Piptadenia, thanks to immunocytochemical analyses. These data are discussed in terms of the evolutionary position of the newly circumscribed mimosoid clade within the Caesalpinioid subfamily and its relative proximity to non-nodulated (but AMF-associated) basal subfamilies.
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Fabaceae/fisiología , Micorrizas/fisiología , Nodulación de la Raíz de la Planta/fisiología , Nódulos de las Raíces de las Plantas/microbiología , Biodiversidad , Filogenia , Simbiosis , Árboles/fisiologíaRESUMEN
During a survey of root-nodulating symbionts of Mimosoid species in the south-east region of Brazil, eight Paraburkholderia isolates were obtained from nodules of the legume species Piptadenia gonoacantha, either from the field or following a soil trapping method with the same plant host. 16S rRNA gene as well as recA and gyrB phylogenetic markers placed these strains in two new clades within the genus Burkholderia sensu lato. DNA-DNA hybridization values and analyses of average nucleotide identities of the whole genome sequence of selected strains in each clade (STM 7183 and STM 7296) showed that the two clades represented novel species of the genus Paraburkholderia. All eight isolates were further characterized using DNA base content determination, chemotaxonomic and biochemical profiling and symbiotic properties, which allowed to distinguish the novel species from known diazotrophic species of the genus Paraburkholderia. Based on genomic and phenotypic data, the names Paraburkholderia piptadeniae sp. nov. with type strain STM 7183T (=DSM 101189T=LMG 29163T) and Paraburkholderia ribeironis sp. nov. with type strain STM 7296T (=DSM 101188T=LMG 29351T) are proposed.
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Burkholderia/clasificación , Fabaceae/microbiología , Filogenia , Nódulos de las Raíces de las Plantas/microbiología , Técnicas de Tipificación Bacteriana , Composición de Base , Brasil , Burkholderia/genética , Burkholderia/aislamiento & purificación , ADN Bacteriano/genética , Genes Bacterianos , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , SimbiosisRESUMEN
INTRODUCTION: To report long term toxicity and efficacy of patients with intermediate risk prostate cancer treated with moderate hypofractionated radiotherapy (HypoRT). MATERIALS AND METHODS: We studied the first consecutive 100 men with intermediate risk (stage T2b-T2c, or PSA = 10-20 ug/L, or Gleason score = 7) adenocarcinoma of the prostate treated between October 2002 and May 2010 in our institution with moderate HypoRT. Patients were treated using three-dimensional conformal HypoRT to a dose of 66 Gy in 22 daily fractions prescribed to the isocenter. Androgen suppression was not given to any patient. A uniform 7 mm margin was created around the prostate for the planning target volume. Daily ultrasound was used to guide the radiotherapy. Common Terminology Criteria for Adverse Events, version 3.0, was used to prospectively score toxicity. Biochemical failure was defined as the nadir PSA level plus 2 ng/m. RESULTS: After a median follow up time of 80 months (range: 7-152), the 8 year actuarial freedom from biochemical relapse survival rate was 90%. The 8 year cancer specific survival and overall survival rates were 96% and 84%, respectively. Only 2 patients died from prostate cancer. The worst grade ≥ 2 late genitourinary (GU) or gastrointestinal (GI) toxicities ever documented were 19% and 20%, respectively. At the last follow up the incidence of grade ≥ 2 late GI or GU toxicity was of only 2% and 3%, respectively. No grade 4 or 5 late toxicity was seen. CONCLUSION: Our long term experience with HypoRT delivering 66 Gy/22 fractions prescribed to the isocenter using three-dimensional conformal radiotherapy shows excellent tumor control with acceptable toxicity.
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Adenocarcinoma/radioterapia , Próstata/patología , Neoplasias de la Próstata/radioterapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Anciano , Anciano de 80 o más Años , Biopsia , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/mortalidad , Quebec/epidemiología , Radioterapia de Intensidad Modulada , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
INTRODUCTION: Surgery and luteinizing hormone-releasing hormone (LHRH) analogs are standard androgen deprivation treatments (ADT) for patients with advanced prostate cancer. We performed a phase I study to explore if irradiation to the testes could be used as an alternative to ADT. MATERIALS AND METHODS: All patients had advanced prostate cancer with normal testosterone levels before treatment and indication for long term castration. Treatment started with one LHRH analog injection (to induce a fast drop of testosterone) followed by irradiation to the whole scrotum. Two fractionation regimens were tested: 17 Gy in 2 fractions, and 24 Gy in 3 fractions. Hormonal blood evaluation was performed before and every 3 months after radiotherapy. Toxicity was evaluated at each visit by the CTCv3 scoring system. This was an IRB approved prospective study. RESULTS: The first three patients received 17 Gy in 2 fractions. None of them developed acute or late skin toxicity and none became castrated, keeping normal levels of testosterone during the time they were followed at 11, 24 and 36 months post-radiotherapy. Another four patients received 24 Gy in 3 fractions. Two developed grade 1 temporary acute dermatitis and, again, none of them became castrated during follow up of 11-36 months. CONCLUSIONS: Prospective studies assessing the effect of the Leydig cells after direct irradiation to the testes are rare. The two radiotherapy regimens used in this study were well tolerated, but not capable of causing castration after 11-36 months of follow up. It is not yet clear whether radiation treatment can effectively induce castration in men.
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Castración/métodos , Fraccionamiento de la Dosis de Radiación , Células Intersticiales del Testículo/efectos de la radiación , Neoplasias de la Próstata/terapia , Traumatismos por Radiación/etiología , Radiodermatitis/etiología , Anciano , Hormona Liberadora de Gonadotropina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias de la Próstata/sangre , Radioterapia/efectos adversos , Testosterona/sangreRESUMEN
BACKGROUND: Burkholderia species play an important ecological role related to xenobiosis, the promotion of plant growth, the biocontrol of agricultural diseases, and symbiotic and non-symbiotic biological nitrogen fixation. Here, we highlight our study as providing the first complete genome of a symbiotic strain of B. phenoliruptrix, BR3459a (=CLA1), which was originally isolated in Brazil from nodules of Mimosa flocculosa and is effective in fixing nitrogen in association with this leguminous species. RESULTS: Genomic comparisons with other pathogenic and non-pathogenic Burkholderia strains grouped B. phenoliruptrix BR3459a with plant-associated beneficial and environmental species, although it shares a high percentage of its gene repertoire with species of the B. cepacia complex (Bcc) and "pseudomallei" group. The genomic analyses showed that the bce genes involved in exopolysaccharide production are clustered together in the same genomic region, constituting part of the Group III cluster of non-pathogenic bacteria. Regarding environmental stresses, we highlight genes that might be relevant in responses to osmotic, heat, cold and general stresses. Furthermore, a number of particularly interesting genes involved in the machinery of the T1SS, T2SS, T3SS, T4ASS and T6SS secretion systems were identified. The xenobiotic properties of strain BR3459a were also investigated, and some enzymes involved in the degradation of styrene, nitrotoluene, dioxin, chlorocyclohexane, chlorobenzene and caprolactam were identified. The genomic analyses also revealed a large number of antibiotic-related genes, the most important of which were correlated with streptomycin and novobiocin. The symbiotic plasmid showed high sequence identity with the symbiotic plasmid of B. phymatum. Additionally, comparative analysis of 545 housekeeping genes among pathogenic and non-pathogenic Burkholderia species strongly supports the definition of a new genus for the second branch, which would include BR3459a. CONCLUSIONS: The analyses of B. phenoliruptrix BR3459a showed key property of fixing nitrogen that together with genes for high tolerance to environmental stresses might explain a successful strategy of symbiosis in the tropics. The strain also harbours interesting sets of genes with biotechnological potential. However, the resemblance of certain genes to those of pathogenic Burkholderia raise concerns about large-scale applications in agriculture or for bioremediation.
Asunto(s)
Burkholderia/genética , Mimosa/microbiología , Proteínas Bacterianas/genética , Sistemas de Secreción Bacterianos , Farmacorresistencia Bacteriana , Genoma Bacteriano , Fijación del Nitrógeno/genética , Fenotipo , Filogenia , Plásmidos/genética , Análisis de Secuencia de ADN , Simbiosis , Sintenía , Factores de Virulencia/genéticaRESUMEN
We assessed, in a field experiment, the effects of arbuscular mycorrhizal fungi (Rhizophagus intraradices) and plant growth-promoting bacteria (Azospirillum brasilense) on the soil biological activity and the growth of key pioneer species used in the revegetation of coal-mining areas undergoing recovery. We applied four inoculation treatments to the pioneer plant species (Lablab purpureus, Paspalum notatum, Crotalaria juncea, Neonotonia wightii, Stylosanthes guianensis, Andropogon gayanus and Trifolium repens) used in the recovery process: NI (Control - Non-inoculated), AZO (A. brasilense), AMF (R. intraradices), and co-inoculation of AZO and AMF. On the 75th and 180th days, we measured plant dry mass, mycorrhizal colonization, N and P concentration, and accumulation in plant tissue. We collected soil to quantify glomalin content and soil enzyme activity. After 180 days, we did a phytosociological characterization of the remaining spontaneous plants.The both microorganisms, singly or co-inoculated, promoted increases in different fractions of soil glomalin, acid phosphatase activity, and fluorescein diacetate activity at 75 and 180 days. The inoculation was linked to higher plant biomass production (62-89%) and increased plant P and N accumulation by 34-75% and 70-85% at 180 days, compared with the non-inoculated treatment. Among the pioneer species sown Crotalaria juncea produced the highest biomass at the 75th and 180th days (67% and 76% of all biomass), followed by Lablab purpureus (3% and 0.5%), while the other species failed to establish. At 180 days, we observed twenty spontaneous plant species growing in the area, primarily from the Poaceae family (74%). That suggests that the pioneer species present in the area do not hinder the ecological succession process. Inoculation of R. intraradices and A. brasilense, isolated or combined, increases soil biological activity, growth, and nutrient accumulation in key pioneer plant species, indicating the potential of that technique for the recovery of lands degraded by coal mining.
RESUMEN
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.NRG Oncology RTOG 0415 is a randomized phase III noninferiority (NI) clinical trial comparing conventional fractionation (73.8 Gy in 41 fractions) radiotherapy (C-RT) with hypofractionation (H-RT; 70 Gy in 28) in patients with low-risk prostate cancer. The study included 1,092 protocol-eligible patients initially reported in 2016 with a median follow-up of 5.8 years. Updated results with median follow-up of 12.8 years are now presented. The estimated 12-year disease-free survival (DFS) is 56.1% (95% CI, 51.5 to 60.5) for C-RT and 61.8% (95% CI, 57.2 to 66.0) for H-RT. The DFS hazard ratio (H-RT/C-RT) is 0.85 (95% CI, 0.71 to 1.03), confirming NI (P < .001). Twelve-year cumulative incidence of biochemical failure (BF) was 17.0% (95% CI, 13.8 to 20.5) for C-RT and 9.9% (95% CI, 7.5 to 12.6) for H-RT. The HR (H-RT/C-RT) comparing biochemical recurrence between the two arms was 0.55 (95% CI, 0.39 to 0.78). Late grade ≥3 GI adverse event (AE) incidence is 3.2% (C-RT) versus 4.4% (H-RT), with relative risk (RR) for H-RT versus C-RT 1.39 (95% CI, 0.75 to 2.55). Late grade ≥3 genitourinary (GU) AE incidence is 3.4% (C-RT) versus 4.2% (H-RT), RR 1.26 (95% CI, 0.69 to 2.30). Long-term DFS is noninferior with H-RT compared with C-RT. BF is less with H-RT. No significant differences in late grade ≥3 GI/GU AEs were observed between assignments (ClinicalTrials.gov identifier: NCT00331773).