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In regions where water is a limited resource, lettuce production can be challenging. To address this, water management strategies like deficit irrigation are used to improve water-use efficiency in agriculture. Associating this strategy with silicon (Si) application could help maintain adequate levels of agricultural production even with limited water availability. Two lettuce crop cycles were conducted in a completely randomized design, with a factorial scheme (2 × 3), with three irrigation levels (60%, 80% and 100%) of crop evapotranspiration (ETc), and with and without Si application. To explore their combined effects, morphological, productive, physiological and nutritional parameters were evaluated in the crops. The results showed that deficit irrigation and Si application had a positive interaction: lettuce yield of the treatment with 80% ETc + Si was statistically similar to 100% ETc without Si in the first cycle, and the treatment with 60% ETc + Si was similar to 100% ETc without Si in the second cycle. Photosynthetic rate, stomatal conductance, intercellular CO2 concentration, transpiration rate and total chlorophyll content increased under water-stress conditions with Si application; in the first cycle, the treatment with 80% ETc + Si increased by 30.1%, 31.3%, 7.8%, 28.46% and 50.3% compared to the same treatment without Si, respectively. Si application in conditions of water deficit was also beneficial to obtain a cooler canopy temperature and leaves with higher relative water content. In conclusion, we found that Si applications attenuate water deficit effects and provide a strategy to ameliorate the yield and water productivity in lettuce crops, contributing to more sustainable practices in agriculture.
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In this Letter, we introduce a concept to produce high-resolution, highly integrable biosensing devices. Our idea exploits the highly absorbing modes in multilayered metamaterials to maximize the transverse magneto-optical Kerr effect (TMOKE). Results are discussed in the context of dielectric uniaxial (ε eff,⥠ε eff,â¥>0) and hyperbolic metamaterial (ε eff,⥠ε eff,â¥<0) regimes. For applications in gas sensing, we obtained sensitivities of S = 46.02 deg/RIU and S = 73.91 deg/RIU when considering the system working in the uniaxial and hyperbolic regimes, respectively, with figures of merit (resolution) in the order of 310 or higher. On the contrary, when considering the system for biosensing applications (incidence from an aqueous medium), we observed that the proposed mechanism can only be successfully used in the uniaxial regime, where a sensitivity of 56.87 deg/RIU was obtained.
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Objetivo: Identificar las causas de exclusión de los donantes renales vivos en un centro hospitalario de tercer nivel en el noroeste de México. Materiales y métodos: Estudio de tipo observacional, transversal, descriptivo, retrospectivo. Se realizó la evaluación de los expedientes clínicos de los candidatos vivos para donación renal, que abarcó el periodo comprendido entre el 1 de enero de 2019 y el 31 de diciembre de 2021. Resultados: De los 30 expedientes seleccionados, solo se eligieron 2 (6,6 %) donadores, es decir, existió un índice de rechazo de 28 (93,3 %) de los potenciales candidatos. La edad promedio fue de 40,7 años; al dividirlos en grupos de edad, se observó que el 7,44 % fueron ≤39 años; el 5,31 %, ≥50 años; y el 4,25 %, de 40 a 49 años. Dentro de las principales patologías que originaron el rechazo del donador vivo se encuentran las enfermedades crónicas, como afección renal desconocida, obesidad, diabetes mellitus, hipertensión arterial sistémica y cardiopatías, que representaron el 60,7 %. El deseo de donar es más frecuente entre consanguíneos que en no consanguíneos. En el caso de los consanguíneos, es decir, hermanos, padres, hijos, tíos, etc., el 64,2 % fue rechazado; en los no consanguíneos, el 34,7 %, que incluía a esposos y amigos. Conclusiones: Los resultados obtenidos sobre el índice de masa corporal (IMC) mostraron que el sobrepeso y la obesidad fueron las principales causas de exclusión, circunstancia que es particular en nuestro país respecto a su perfil epidemiológico. La cantidad de donantes vivos en nuestro centro se redujo porque la mayor parte de la población no es sana, padece obesidad y ello repercute al momento de presentarse como candidato a donante.
Objective: To identify the causes for exclusion of living kidney donors at a third-level hospital in northwestern Mexico. Materials and methods: An observational, cross-sectional, descriptive and retrospective study, in which the medical records of candidates for living kidney donation were evaluated from January 1, 2019 to December 31, 2021. Results: Out of the 30 selected records, only 6.6 % (2) were chosen as donors, i.e., the rejection rate of the potential candidates was 93.3 % (28). The average age was 40.7 years; when divided into age groups, it was observed that 7.44 % were ≤ 39 years, 5.31 % were ≥ 50 years and 4.25 % were in the 40-49 age range. The main pathologies that caused the rejection of living donors were chronic diseases such as unknown renal disease, obesity, diabetes mellitus, systemic hypertension and heart diseases, which accounted for 60.7 %. The desire to donate was more frequent among blood relatives than non-blood relatives. In the case of blood relatives, i.e., siblings, parents, children, uncles, aunts, etc., 64.2 % were rejected, while 34.7 % of non-blood relatives, including spouses and friends, were rejected. Conclusions: Based on the body mass index (BMI), the results showed that overweight and obesity were the main causes of exclusion, a situation that is consistent with the Mexican epidemiological profile. The number of living donors at our center has been reduced because most of the population is not healthy and has obesity, which affects the willingness to be a candidate for living kidney donation.
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We demonstrate a concept for the active manipulation of radiated fields by a magnetoplasmonic half-wave dipole nanoantenna. Our idea comprises a two arms nanoantenna, made of metallic ferromagnetic cobalt-silver alloy (Co6Ag94), inspired by the analogous radio frequency half-wave dipole antenna design. Numerical results, obtained under the magnetization saturation condition, indicate a tilting of the radiated beam depending on the magnitude and sense of the magnetization of the ferromagnetic material. Significantly, we obtained tilting angles as large as ±9.7∘ around the y axis for the magnetization placed along the x or z axes, respectively. Results in this work not only open up a new, to the best of our knowledge, way to dynamically manipulate the beam steering at the chip-scale, but also contribute to unveil novel magneto-optical effects at the nanoscale.
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Introdução: A pandemia de coronavírus (COVID-19) impactou não apenas a saúde física, em decorrência da síndrome respiratória aguda grave causada pelo vírus, mas também impactou a saúde mental, as áreas econômica e a social. Além disso, o foco do cenário pandêmico foi a contingência do COVID-19, o que propiciou o aparecimento ou o agravamento de outras doenças. Dessa forma, os escopos originados da pandemia tornaram-se potenciais desencadeantes de quadros de estresse e de interferência na qualidade de vida da população. Proposição: avaliar o índice de estresse percebido e a qualidade de vida da população em dois grupos de pessoas: primeiro, as que tiveram diagnóstico confirmado de COVID-19 e, segundo indivíduos que não contraíram a doença. Materiais e Métodos: Participaram da pesquisa 66 indivíduos, entre 18 e 60 anos, sendo 33 de pessoas sem contaminação e 33 pessoas que tiveram diagnóstico confirmado. Os participantes responderam dois questionários: O questionário de estresse percebido (QEP), para avaliar o estresse e outro questionário para avaliação da qualidade de vida (SF-36). Resultados: A análise mostrou que o QEP dos indivíduos não contaminados foi menor (0,64 + 0,04); em comparação aos indivíduos que tiveram o resultado positivo para doença (0,73 + 0,02) (p = 0,0484), diferença estatisticamente significativa, o que mostra que os casos positivos têm percepção que estão mais estressados. Na análise do SF-36, apenas o domínio Capacidade Funcional apresentou diferença estatisticamente significativa, sendo que os voluntários que não tiveram a doença apresentaram um maior valor (93,3 + 2,0), que os contaminados (73,0 + 3,6) (p < 0,0001), o que sugere melhor qualidade de vida aos primeiros. Conclusão: O estudo apresenta resultados que indicam que a pandemia impactou negativamente a saúde da população, pois os participantes diagnosticados com COVID-19 tiveram maior estresse percebido e menor qualidade de vida, em comparação aos não contaminados.
Introduction: The coronavirus pandemic (COVID-19) has not only impacted physical health, as result of the severe acute respiratory syndrome caused by the virus, but has also impacted mental health, the economic and social areas. In addition, the focus of pandemic scenario was the COVID-19 contingency, which led to the appearance or worsening of other diseases. Besides the scopes originated from the pandemic became potential triggers of stress and interference in the population's quality of life. Proposition: to evaluate the perceived stress index and the population's quality of life in two groups of people: first, those who had a confirmed diagnosis of COVID-19 and, second, individuals who did not contract the disease. Materials and Methods: 66 individuals participated in the research, between 18 and 60 years old, being 33 people without contamination and 33 people who had a confirmed diagnosis. Participants answered two questionnaires: The Perceived Stress Questionnaire (QEP) to assess stress and another questionnaire to assess quality of life (SF-36). Results: The analysis of the results showed that the QEP of non-contaminated individuals was lower (0.64 + 0.04) than that of individuals who tested positive for the disease (0.73 + 0.02) (p = 0.0484), statistically significant difference, which shows that positive cases are perceived to be more stressed. In the analysis of SF-36, only the Functional Capacity domain showed statistically significant difference, and the volunteers who did not have the disease presented higher value (93.3 + 2.0) than contaminated individuals (73.0 + 3.6) (p < 0.0001), suggesting better quality of life. Conclusion: The study presents results that indicate the pandemic negatively impacted the health of the population, as participants diagnosed with COVID-19 had greater perceived stress and lower quality of life, compared to non-contaminated ones.
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The design of optoelectronic devices made with ZnO superlattices requires the knowledge of the refractive index, which currently can be done only for films thicker than 30 nm. In this work, we present an effective medium approach to determine the refractive index of ZnO layers as thin as 2 nm. The approach was implemented by determining the refractive index of ZnO layers ranging from 2 nm to 20 nm using spectroscopic ellipsometry measurements in multilayers. For a precise control of morphology and thickness, the superlattices were fabricated with atomic layer deposition (ALD) with alternating layers of 2 nm thick Al2O3 and ZnO, labeled as N ZnO-Al2O3, where N = 10, 20, 30, 50, 75 and 100. The total thickness of all superlattices was kept at 100 nm. The approach was validated by applying it to similar superlattices reported in the literature and fitting the transmittance spectra of the superlattices.
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Leucine-rich repeat kinase 2 (LRRK2) is the most commonly mutated gene in familial Parkinson's disease1 and is also linked to its idiopathic form2. LRRK2 has been proposed to function in membrane trafficking3 and colocalizes with microtubules4. Despite the fundamental importance of LRRK2 for understanding and treating Parkinson's disease, structural information on the enzyme is limited. Here we report the structure of the catalytic half of LRRK2, and an atomic model of microtubule-associated LRRK2 built using a reported cryo-electron tomography in situ structure5. We propose that the conformation of the LRRK2 kinase domain regulates its interactions with microtubules, with a closed conformation favouring oligomerization on microtubules. We show that the catalytic half of LRRK2 is sufficient for filament formation and blocks the motility of the microtubule-based motors kinesin 1 and cytoplasmic dynein 1 in vitro. Kinase inhibitors that stabilize an open conformation relieve this interference and reduce the formation of LRRK2 filaments in cells, whereas inhibitors that stabilize a closed conformation do not. Our findings suggest that LRRK2 can act as a roadblock for microtubule-based motors and have implications for the design of therapeutic LRRK2 kinase inhibitors.
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Microscopia Crioeletrônica , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/química , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Microtúbulos/química , Microtúbulos/metabolismo , Doença de Parkinson/metabolismo , Benzamidas/farmacologia , Biocatálise/efeitos dos fármacos , Dimerização , Dineínas/antagonistas & inibidores , Dineínas/metabolismo , Humanos , Cinesinas/antagonistas & inibidores , Cinesinas/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/antagonistas & inibidores , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/ultraestrutura , Microtúbulos/ultraestrutura , Modelos Moleculares , Movimento/efeitos dos fármacos , Ligação Proteica , Domínios Proteicos/efeitos dos fármacos , Pirazóis/farmacologia , Repetições WD40RESUMO
Children and adolescents with haematological malignancies (PedHM) are characterized by a severe loss of exercise ability during cancer treatment, lasting throughout their lives once healed and impacting their social inclusion prospects. The investigation of the effect of a precision-based exercise program on the connections between systems of the body in PedHM patients is the new frontier in clinical exercise physiology. This study is aimed at evaluating the effects of 11 weeks (3 times weekly) of combined training (cardiorespiratory, resistance, balance and flexibility) on the exercise intolerance in PedHM patients. Two-hundred twenty-six PedHM patients were recruited (47% F). High or medium frequency participation (HAd and MAd) was considered when a participant joined; > 65% or between 30% and < 64% of training sessions, respectively. The "up and down stairs'' test (TUDS), "6 min walking" test (6MWT), the "5 Repetition Maximum strength" leg extension and arm lateral raise test (5RM-LE and 5RM-ALR), flexibility (stand and reach), and balance (stabilometry), were performed and evaluated before and after training. The TUDS, the 5RM-LE and 5RM-ALR, and the flexibility exercises showed an increase in HAd and MAd groups (P < 0.05), while the 6MWT and balance tests showed improvement only in HAd group (P < 0.0001). These results support the ever-growing theory that, in the case of the treatment of PedHM, 'exercise is medicine' and it has the potential to increase the patient's chances of social inclusion.
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Terapia por Exercício , Neoplasias Hematológicas/fisiopatologia , Neoplasias Hematológicas/terapia , Força Muscular , Aptidão Física , Equilíbrio Postural , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Medicina de PrecisãoRESUMO
BACKGROUND: Alcohol use disorders have a prevalence of 10% among the population of the United States and Europe and are one of the most frequent causes of liver cirrhosis in the Western world. Currently, alcohol-related liver cirrhosis represents one of the most frequent indications to liver transplant (LT), both as independent cause or associated with hepatitis C virus or hepatitis B virus infections. Starting from 2014, a multidisciplinary team involving surgeons, gastroenterologists, clinical toxicologists, psychiatrists, and psychologists was developed within the Modena Liver Transplant Center. METHODS: We retrospectively reviewed our prospectively maintained institutional database of liver transplants in order to identify cirrhotic patients eligible for LT with a diagnosis of alcohol use disorder. RESULTS: A total of 756 liver transplants were performed at Policlinico University Hospital, University of Modena, and Reggio Emilia, MO, Italy, between November 2000 and November 2017; 102 patients who underwent LT were considered eligible for inclusion in the study. CONCLUSIONS: The multidisciplinary approach, together with blood, urinary, and hair tests, allows identification of early recurrences and improves survival. Further studies are necessary to understand how multidisciplinary teams can change the 6-month rule in patient selection.
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Alcoolismo/diagnóstico , Cirrose Hepática Alcoólica/cirurgia , Transplante de Fígado , Seleção de Pacientes , Adulto , Abstinência de Álcool , Feminino , Humanos , Itália , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Reincidência , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Estados UnidosRESUMO
A new octave bandwidth high selectivity compact microstrip diplexer working in the band from 10 to 20 GHz is presented, intended to be a part of an electro-optical interferometer covering the whole frequency band. The circuit is based on the combination of hybrid couplers and bandpass filters both on the microstrip technology. The diplexer provides two output frequency bands which cover the 10-14 GHz (relative bandwidth of 33%) and the 16-20 GHz (relative bandwidth of 22%) ranges, respectively, with a stop band in between from 14 to 16 GHz. Measured results show a insertion loss level of 3.3 dB for both output bands and high selectivity performance, exhibiting a rejection level between output bands higher than 20 dB and return loss better than 10 dB in all ports.
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BACKGROUND: HER2 over-expression is related with a poor prognosis in patients with invasive breast cancer tumors. Clinical associations have reported that somatic mutations of p53 more frequently detected in cases of sporadic breast cancer of the HER2 subtypes, besides a high percentage of HER2-amplifying tumors carry germline mutations of p53. The mechanisms responsible for the acquisition of oncogenic functions of p53 mutant proteins (mtp53), known as Gain of Function (GOF), over HER2 expression have not been reported. The objective of this study was to evaluate a possible relationship between p53 mutants and HER2 regulation. METHODS: HER2 expression (transcription and protein), as well as HER2 protein stabilization have been evaluated after inducing or silencing of p53 mutants' expression in cell lines. Finally, we evaluated the interaction of the p53 mutants over the HER2 receptor promoter. RESULTS: Higher HER2 expression in cell lines harboring endogenous mtp53 compared with wt or null expression of p53 cell lines. Transfection of p53 mutants (R248Q and R273C) in cell lines increased the expression of HER2. Silencing of p53 mutants, decrease HER2 expression. The p53 mutants R248Q and R273C significantly increase the luciferase activity on the HER2 promoter, and both mutants also promote acetylation of H3 and H4 histones binding in it. CONCLUSIONS: These findings show for the first time that p53 mutants induce over-expression of HER2 at transcriptional level of the HER2 protein. Our results could have clinical implications in breast cancer and other types of cancer where HER2 is over-expressed and used as a therapy target.
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Mutação com Ganho de Função , Receptor ErbB-2/genética , Proteína Supressora de Tumor p53/genética , Acetilação , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Humanos , Regiões Promotoras GenéticasRESUMO
BACKGROUND: The efficacy of direct-acting anti-viral (DAA) therapy in patients with a history of hepatocellular carcinoma (HCC) is unknown. AIM: We prospectively evaluated whether previously treated HCC affects DAA efficacy in a large real-life cohort of cirrhotic patients. METHODS: From January to December 2015 all consecutive HCV mono-infected patients with cirrhosis and/or history of HCC attending 10 Italian tertiary liver centres were enrolled. Baseline characteristics and response to therapy were recorded. 1927 patients were enrolled (mean age: 62.1 ± 10.9 years; 1.205 males). Genotype 1 was the most frequent (67.9%) followed by genotypes 3 (12.4%), 2 (11.2%) and 4 (8.6%). 88.4% and 10.9% of cases were classified Child A and B, respectively, and 14 (<1%) cases were classified Child C. Ascites and hepatic encephalopathy occurred in 10.7% and 3.2% of patients, respectively. Varices were detected in 39.3% of patients. Suboptimal and optimal treatment was prescribed: 15.9% of patients received sofosbuvir/simeprevir, 33.4% sofosbuvir/ledipasvir, 20.2% a Viekirax + Exviera regimen, 15.7% sofosbuvir/ribavirin, 9.9% sofosbuvir/daclatasvir and 3.4% Viekirax; 1.3% of patients received an interferon-based regimen. RESULTS: The sustained virologic response (SVR) rate at intention-to-treat analysis was 95.1%. It differed significantly across Child classes, that is, 96.3%, 86.1% and 71.4% Child A, B and C, respectively (P < 0.0001) and across genotypes (P = 0.002). The SVR rate did not differ between patients with (95.0%) and those without previous HCC (95.1%). At multivariable analysis, SVR was significantly associated with HCV genotype, Child class. CONCLUSION: This large real-life study proves that the efficacy of DAA in cirrhotic patients is not impaired by successfully treated HCC.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Idoso , Benzimidazóis/administração & dosagem , Carbamatos , Carcinoma Hepatocelular/etiologia , Estudos de Coortes , Quimioterapia Combinada , Feminino , Fluorenos/administração & dosagem , Genótipo , Hepacivirus/genética , Encefalopatia Hepática/epidemiologia , Humanos , Imidazóis/administração & dosagem , Interferons/uso terapêutico , Itália , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirrolidinas , Ribavirina/uso terapêutico , Simeprevir/administração & dosagem , Sofosbuvir/uso terapêutico , Resposta Viral Sustentada , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/análogos & derivados , Valina/análogos & derivadosRESUMO
Resveratrol (RES), a polyphenol compound with antiproliferative properties, has been previously evaluated for its beneficial effects against a variety of tumour cells. The current study elucidated the means by which RES enhances the antiproliferative effects of cisplatin (CIS) on MCF7 cells, focusing on the inhibitory effects on DNA repair of doublestrand breaks (DSBs). Chemoresistant MCF7 cells (MCF7R) were generated by continuous exposure to low concentrations of CIS (10 µM CISIC40) during 5 passages, with the IC50 value increasing ~3fold. Using an MTT assay, we estimated the changes in IC50 for CIS in MCF7, T47D, MDAMB231 and MCF7R cells in the presence of RES. The relative transcript level of Nbs1, Mre11 and Rad50 genes was assessed using RTqPCR analysis. Rad51 and H2AX [pSer139] protein expression was determined by western blot analysis. RES at 50 and 100 µM significantly enhanced the antiproliferative effects of CIS in both MCF7 and MCF7R cells, decreasing the IC50 values for CIS to onetenth and onesixth, respectively. A total of 100 µM RES decreased the relative transcript levels of homologous recombination (HR) initiation complex components and the Rad51 protein level in MCF7 and MCF7R cells. After 48 h of CIS DNA damage, the levels of Rad51 protein increased, but this effect was inhibited by 100 µM RES. RES also maintained serine 139 phosphorylation of histone H2AX, suggesting that RES prevents the repair of DSBs. It was observed that RES exerts an antagonistic effect over CIS on the activation of Rad51 and sustained phosphorylation of H2AX. The results suggest that RES in combination with DNA damagebased therapy has potential as a strategy to overcome resistance and provide much safer and more effective treatment for breast cancer.
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Neoplasias da Mama/genética , Cisplatino/farmacologia , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Rad51 Recombinase/genética , Estilbenos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , Células MCF-7 , Fosforilação/efeitos dos fármacos , Rad51 Recombinase/metabolismo , ResveratrolRESUMO
A 30% bandwidth phase shifter with four phase states is designed to be integrated in a radio astronomy receiver. The circuit has two 90° out-of-phase microwave phase-shifting branches which are combined by Wilkinson power dividers. Each branch is composed of a 180° phase shifter and a band-pass filter. The 180° phase shifter is made of cascaded hybrid rings with microwave PIN diodes as switching devices. The 90° phase shift is achieved with the two band-pass filters. Experimental characterization has shown significant results, with average phase shift values of -90.7°, -181.7°, and 88.5° within the operation band, 35-47 GHz, and mean insertion loss of 7.4 dB. The performance of its integration in a polarimetric receiver for radio astronomy is analyzed, which validates the use of the presented phase shifter in such type of receiver.
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AIMS: The aim of this phase II study was to evaluate the efficacy and toxicity of stereotactic body radiotherapy in patients with low or intermediate risk prostate cancer. MATERIALS AND METHODS: Biopsy-confirmed prostate cancer patients were enrolled, provided that they had the following characteristics: initial prostate-specific antigen (PSA) ≤ 20 ng/ml, Gleason Score < 7, International Prostate Symptom Score < 7. The treatment schedule was 35 Gy in five fractions, delivered with volumetric modulated arcs with flattening filter free beams. Toxicity was recorded according to CTCAE criteria v4.0. Biochemical failure was calculated according to the Phoenix definition. The Expanded Prostate Cancer Index Composite questionnaire was used to record health-related quality of life. RESULTS: Between December 2011 and March 2015, 90 patients were enrolled (53 low risk, 37 intermediate risk). The median age was 71 years (range 48-82). In total, 58 (64.5%) of the patients had Gleason Score=6, the remaining had Gleason Score=7.The median initial PSA was 6.9 ng/ml (range 2.7-17.0). Acute toxicity was mild, with 32.2 patients presenting grade 1 urinary toxicity and 32.2% of patients presenting grade 2 urinary toxicity, mainly represented by urgency, dysuria and stranguria. Rectal grade 1 toxicity was found in 15.5% of patients, whereas grade 2 toxicity was recorded in 6.6% of patients. Regarding late toxicity, grade 1 proctitis was recorded in 11.1% of patients and grade 1 urinary in 38.8%; only two events of grade 2 urinary toxicity were observed (transient urethral stenosis, resolved by a 24 h catheterisation). At a median follow-up of 27 months (6-62 months) only two intermediate risk patients experienced a biochemical failure. Health-related quality of life revealed a slight worsening in all the domains during treatment, with a return to baseline 3 months after treatment. CONCLUSIONS: Stereotactic body radiotherapy delivered using linac-based flattening filter free volumetric modulated arc radiotherapy in low and intermediate risk prostate cancer patients is associated with mild toxicity profiles and good patient-reported quality of life.
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Neoplasias da Próstata/radioterapia , Radiocirurgia/métodos , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Aceleradores de Partículas , Antígeno Prostático Específico/sangue , Qualidade de Vida , Radiocirurgia/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Inquéritos e QuestionáriosRESUMO
It is well known that vitamin A and its receptors protect against cancer development and that Retinoid Acid Receptor ß (RARß) is epigenetically silenced during tumoral progression. Cervical Cancer (CC) has been causally linked to high risk human papillomavirus (HR-HPV) infection. However, host factors are important in determining the outcome of persistent HR-HPV infection as most cervical precancerous lesions containing HR-HPVs do not progress to invasive carcinomas. Increasing evidence suggests that low diet in vitamin A and their receptors participate in the development of CC. The aim of this study has been to investigate the effects of abated RARß expression in the development of cervical premalignant lesions in 4 month-old conditional mice (RARß(L-/L-)). Results demonstrated the development of spontaneous squamous metaplasia, inflammatory infiltrate, enhanced mitotic activity, loss of cell differentiation, as well as decreased apoptosis and p16(INK4a) protein levels in RARß(L-/L-) mice cervix. All these changes are hallmarks of moderate dysplasia. Importantly, our results suggest that the low expression of RARß, may induce the down regulation of p16(INK4a), chronic inflammation and decreased apoptosis and may be involved in vulnerability to HR-HPV and early stage cervical carcinogenesis.
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Inflamação/patologia , Lesões Pré-Cancerosas/patologia , Receptores do Ácido Retinoico/metabolismo , Neoplasias do Colo do Útero/patologia , Animais , Apoptose , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Colo do Útero/patologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Feminino , Imunofluorescência , Deleção de Genes , Humanos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores do Ácido Retinoico/genética , Displasia do Colo do Útero/patologia , Vagina/patologiaRESUMO
This work is focused on the design, fabrication, and performance analysis of a square-law Schottky diode detector based on lossy transmission lines working under cryogenic temperature (15 K). The design analysis of a microwave detector, based on a planar gallium-arsenide low effective Schottky barrier height diode, is reported, which is aimed for achieving large input return loss as well as flat sensitivity versus frequency. The designed circuit demonstrates good sensitivity, as well as a good return loss in a wide bandwidth at Ka-band, at both room (300 K) and cryogenic (15 K) temperatures. A good sensitivity of 1000 mV/mW and input return loss better than 12 dB have been achieved when it works as a zero-bias Schottky diode detector at room temperature, increasing the sensitivity up to a minimum of 2200 mV/mW, with the need of a DC bias current, at cryogenic temperature.
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The occurrence of peritoneal carcinomatosis is a major cause of treatment failure in colorectal cancer and is considered incurable. However, new therapeutic approaches have been proposed, including cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Although HIPEC has been effective in selected patients, it is not known how HIPEC prolongs a patient's lifespan. Here, we have demonstrated that HIPEC-treated tumor cells induce the activation of tumor-specific T cells and lead to vaccination against tumor cells in mice. We have established that this effect results from the HIPEC-mediated exposure of heat shock protein (HSP) 90 at the plasma membrane. Inhibition or blocking of HSP90, but not HSP70, prevented the HIPEC-mediated antitumoral vaccination. Our work raises the possibility that the HIPEC procedure not only kills tumor cells but also induces an efficient anticancer immune response, therefore opening new opportunities for cancer treatment.
Assuntos
Vacinas Anticâncer/farmacologia , Proteínas de Choque Térmico HSP90/metabolismo , Hipertermia Induzida/métodos , Neoplasias Peritoneais/imunologia , Neoplasias Peritoneais/terapia , Animais , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Técnicas de Cocultura , Terapia Combinada , Células Dendríticas/imunologia , Proteínas de Choque Térmico HSP90/genética , Humanos , Camundongos Endogâmicos BALB C , Neoplasias Peritoneais/tratamento farmacológico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Polymorphism of interleukin 28B gene represents a powerful outcome predictor for interferon-based regimens in hepatitis C virus infection. However, some studies report conflicting results. The predictive value of interleukin 28B genotype over the outcome interferon-α/ribavirin treatment was thoroughly evaluated and compared with virological predictors of response. Literature revision was performed on PubMed. Pooled odds ratios (ORs) were calculated by fixed- or random-effects models. Heterogeneity and publication bias were also assessed. Sixty-two eligible papers including 20 290 patients were retrieved. Both polymorphisms (rs12979860 and rs8099917) were strongly associated with response (OR=4.09 and 4.00, respectively), however, the association was weaker for subjects infected with viral genotypes 2 and 3 (OR=1.52 and 1.49, respectively). Compared with interleukin 28B genotype, the association with response was lower for baseline viremia (OR=2.15) and higher for rapid virological response (OR=13.86). These results provide a critical evaluation of interleukin 28B genotype as a pharmacogenetic predictor in hepatitis C patients.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interleucinas/genética , Povo Asiático , Quimioterapia Combinada , Estudos de Associação Genética , Genótipo , Hepacivirus/genética , Hepatite C Crônica/etnologia , Hepatite C Crônica/genética , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Interferons , Razão de Chances , Polietilenoglicóis/uso terapêutico , Polimorfismo de Nucleotídeo Único , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Carga Viral , População BrancaRESUMO
Present study shows that the inclusion of single negative polaritonic-like layers in one-dimensional metamaterial photonic superlattices may lead to new effects, such as the simultaneous existence of omnidirectional zero-n¯ and zero-Ï(eff) non-Bragg gaps for both transversal electric (TE) and transversal magnetic (TM) polarizations, which are also robust to uniaxial anisotropic effects. Such omnidirectional behavior, in the case of the zero-n¯ gap, occurs within the same frequency range for both polarizations, which is not allowed in the case of double negative (DNG) metamaterial-air superlattices, suggesting a route to design and development of omnidirectional optical filters for all polarizations. Furthermore, present results show that, when polaritonic inclusions are considered, the long wavelength approximation is not ever suitable to describe the non-Bragg gap edges.