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MuV caused three epidemic waves in Spain since genotype G emerged in 2005, despite high vaccination coverage. SH gene sequencing according to WHO protocols allowed the identification of seven relevant variants and 88 haplotypes. While the originally imported MuVi/Sheffield.GBR/1.05/-variant prevailed during the first two waves, it was subsequently replaced by other variants originated by either local evolution or importation, according to the additional analysis of hypervariable NCRs. The time of emergence of the MRCA of each MuV variant clade was concordant with the data of the earliest sequence. The analysis of Shannon entropy showed an accumulation of variability on six particular positions as the cause of the increase on the number of circulating SH variants. Consequently, SH gene sequencing needs to be complemented with other more variable markers for mumps surveillance immediately after the emergence of a new genotype, but the subsequent emergence of new SH variants turns it unnecessary.
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Vírus da Caxumba , Caxumba , Humanos , Vírus da Caxumba/genética , Espanha/epidemiologia , Filogenia , Caxumba/epidemiologia , Caxumba/prevenção & controle , GenótipoRESUMO
We demonstrate fast control of the interatomic interactions in a Bose-Einstein condensate by coherently coupling two atomic states with intra- and interstate scattering lengths of opposite signs. We measure the elastic and inelastic scattering properties of the system and find good agreement with a theoretical model describing the interactions between dressed states. In the attractive regime, we observe the formation of bright solitons formed by dressed-state atoms. Finally, we study the response of the system to an interaction quench from repulsive to attractive values, and observe how the resulting modulational instability develops into a bright soliton train.
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OBJECTIVE: The present study evaluated the biological effects and biomineralization potential of a new tantalum oxide (Ta2O5)-containing material designed for vital pulp therapy or perforation repair (NeoMTA 2), compared to NeoMTA Plus and Bio-C Repair. MATERIAL AND METHODS: Human dental pulp stem cells (hDPSCs) were exposed to different eluates from NeoMTA Plus, NeoMTA 2, and Bio-C Repair. Ion release from each material was determined using inductively coupled plasma-optical emission spectrometry (ICP-MS). The biological experiments performed were MTT assays, apoptosis/necrosis assays, adhesion assays, migration assays, morphology evaluation, and reactive oxygen species (ROS) production analysis. Biomineralization was assessed by Alizarin red S staining. Finally, osteo/odontogenic gene expression was determined by real-time quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR). Data were analyzed using one-way ANOVA followed by Tukey's multiple comparison test. RESULTS: NeoMTA 2 displayed a significantly higher calcium release compared to the other materials (p < 0.05). When hDPSCs were cultured in presence of the different material eluates, all groups exhibited similar hDPSC viability and migration rates when compared to untreated cells. Substantial cell attachment and spreading were observed in all materials' surfaces, without significant differences. hDPSCs treated with NeoMTA 2 displayed an upregulation of ALP, Col1A1, RUNX2 (p < 0.001), ON, and DSPP genes (p < 0.05), and showed the highest mineralization potential compared to other groups (p < 0.001). Finally, the more concentrated eluates from these materials, specially NeoMTA Plus and NeoMTA 2, promoted higher ROS production in hDPSCs compared to Bio-C Repair and control cells (p < 0.001), although these ROS levels did not result in increased cell death. CONCLUSIONS: The new tantalum oxide (Ta2O5)-containing material shows an adequate cytocompatibility and the ability to promote biomineralization without using chemical osteogenic inducers, showing great potential as a new material for vital pulp therapy. CLINICAL RELEVANCE: NeoMTA 2 seems to be a promising material for vital pulp therapy. Further studies considering its biocompatibility and biomineralization potential are necessary.
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Cálcio , Cimento de Silicato , Biomineralização , Compostos de Cálcio/farmacologia , Diferenciação Celular , Células Cultivadas , Polpa Dentária , Humanos , Teste de Materiais , Óxidos , Silicatos/farmacologia , Células-Tronco , TantálioRESUMO
OBJECTIVE: The aim of the present study was to evaluate the in vitro biocompatibility of Theracal PT, Theracal LC, and MTA Angelus, considered as bioactive materials used for vital pulp treatment, on human dental pulp stem cells (hDPSCs). MATERIALS AND METHODS: Human dental pulp stem cells (hDPSCs) were isolated from third molars, and material eluates were prepared (undiluted, 1:2, and 1:4 ratios). The hDPSC cytotoxicity, adhesion, morphology, viability, and cell migration were assessed. The mineralization nodule formation was determined by Alizarin red S staining (ARS). The odonto/osteogenic differentiation potential was assessed by osteo/odontogenic marker expression real-time qPCR. The chemical composition and ion release of the vital pulp materials were determined by energy dispersive X-ray (EDX) and inductively coupled plasma-mass spectrometry (ICP-MS), respectively. Statistical differences were assessed by ANOVA and Tukey's test (p < 0.05). RESULTS: The three vital pulp materials showed variable levels of calcium, tungsten, silicon, and zirconium release and in their chemical composition. Cytocompatibility assays revealed higher hDPSC viability and migration rates when treated with Theracal PT than with Theracal LC. The lowest cell adhesion and spreading were observed in all Theracal LC-treated groups, whereas the highest were observed when treated with MTA. Theracal PT and MTA promoted the upregulation of DSPP and RUNX2 gene expression (p < 0.05). After 21 days, both MTA Angelus and Theracal PT-treated cells exhibited a significantly higher mineralized nodule formation than the negative control (p < 0.05). CONCLUSIONS: This study demonstrates the favorable in vitro cytocompatibility and bioactive properties of the recently introduced Theracal PT and the well-established MTA Angelus on hDPSCs, as opposed to Theracal LC. More studies, including in vivo animal testing are suggested before these new formulations might be used in the clinical setting. CLINICAL RELEVANCE: Theracal PT is a new material that could be clinically suitable for vital pulp therapy. Further studies considering its biocompatibility and bioactivity are necessary.
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Osteogênese , Células-Tronco , Compostos de Alumínio , Compostos de Cálcio/farmacologia , Polpa Dentária , Combinação de Medicamentos , Humanos , Teste de Materiais , Óxidos , Silicatos/farmacologiaRESUMO
OBJECTIVE: The aim of this study was to evaluate the microstructural composition, ion release, cytocompatibility, and mineralization potential of Bio-C Sealer ION+ (BCI) and EndoSequence BC Sealer HiFlow (BCHiF), compared with AH Plus (AHP), in contact with human periodontal ligament cells (hPDLCs). MATERIALS AND METHODS: The sealers' ionic composition and release were assessed using energy-dispersive spectroscopy (EDS) and inductively coupled plasma mass spectrometry (ICP-MS), respectively. For the biological assays, hPDLCs were isolated from third molars, and sealer extracts were prepared (undiluted, 1:2, and 1:4 ratios). An MTT assay, wound-healing assay, and cell morphology and adhesion analysis were performed. Activity-related gene expression was determined using RT-qPCR, and mineralization potential was assessed using Alizarin Red staining (ARS). Statistical analyses were performed using one-way ANOVA and Tukey's post hoc test (α < 0.05). RESULTS: The three sealers exhibited variable levels of silicon, calcium, zirconium, and tungsten release and in their composition. Both BCI and BCHiF groups showed positive results in cytocompatibility assays, unlike AHP. The BCHiF group showed an upregulation of CAP (p < 0.01), CEMP1, ALP, and RUNX2 (p < 0.001) compared with the negative control, while the BCI group showed an upregulation of CEMP1 (p < 0.01), CAP, and RUNX2 (p < 0.001). Both groups also exhibited a greater mineralization potential than the negative and positive controls (p < 0.001). CONCLUSIONS: The calcium silicate-based sealers considered in the present in vitro study exhibited a high calcium ion release, adequate cytocompatibility, upregulated osteo/cementogenic gene expression, and increased mineralized nodule formation in contact with hPDLCs. CLINICAL RELEVANCE: From a biological perspective, BCI and BCHiF could be clinically suitable for root canal filling.
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Materiais Restauradores do Canal Radicular , Compostos de Cálcio/farmacologia , Resinas Epóxi , Humanos , Teste de Materiais , Proteínas , Materiais Restauradores do Canal Radicular/farmacologia , Silicatos/farmacologiaRESUMO
BACKGROUND: Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted. OBJECTIVES: We evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016. METHODS: Pre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a ≥ 20% mutant sensitivity cut-off. Those present at 1%-19% of the virus population were considered to be low-frequency variants. RESULTS: From a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants. CONCLUSIONS: Transmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens.
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Infecções por HIV , Inibidores de Integrase de HIV , Integrase de HIV , HIV-1 , Estudos de Coortes , Farmacorresistência Viral , Genótipo , Infecções por HIV/tratamento farmacológico , Integrase de HIV/genética , Inibidores de Integrase de HIV/farmacologia , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/genética , Humanos , Integrases , Mutação , Estudos Prospectivos , Espanha/epidemiologiaRESUMO
In this work, ecotoxicological bioassays based on Lactuca sativa seeds and bioluminescent bacterium (Vibrio fischeri) have been carried out in order to quantify the toxicity of Norfloxacin (NOR) and sodium sulfate solutions, before and after treating them using electrochemical advanced oxidation. The effect of some process variables (anode material, reactor configuration and applied current) on the toxicity evolution of the treated solution has been studied. A NOR solution shows an EC50(5 days) of 336â¯mgâ¯L-1towards Lactuca sativa. This threshold NOR concentration decreases with sodium sulfate concentration, in solutions that contain simultaneously Norfloxacin and sodium sulfate. In every case considered in this work, the electrochemical advanced oxidation process increased the toxicity (towards both Lactuca sativa and Vibrio fischeri) of the solution. This toxicity increase is mainly due to the persulfate formation during the electrochemical treatment. From a final solution toxicity point of view, the best results were obtained using a BDD anode in a divided reactor applying the lowest current intensity.
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Técnicas Eletroquímicas/métodos , Norfloxacino/toxicidade , Poluentes Químicos da Água/toxicidade , Purificação da Água/métodos , Aliivibrio fischeri/efeitos dos fármacos , Boro/química , Cerâmica/química , Diamante/química , Ecotoxicologia , Técnicas Eletroquímicas/instrumentação , Eletrodos , Lactuca/efeitos dos fármacos , Norfloxacino/análise , Oxirredução , Sulfatos/química , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: We conducted a retrospective survey within the European Society for Blood and Marrow Transplantation (EBMT) registry to assess the outcomes of cord blood transplantation (CBT) in secondary acute myeloid leukaemia (sAML). METHODS: Inclusion criteria consisted of ≥18 years of age, sAML, first CBT between 2002 and 2016, and either first complete remission (CR) or active disease at CBT. RESULTS: One hundred forty-six patients met the study inclusion criteria. Status at transplantation was first CR (n = 97), primary refractory sAML (n = 30) or relapsed (n = 19) sAML. Neutrophil engraftment was achieved in 118 patients while the remaining 25 patients (17%) failed to engraft. This includes 13% of patients transplanted in first CR versus 30% of those transplanted with active disease (P = 0.008). Two-year incidences of relapse were 25% in first CR patients versus 36% in those with advanced disease (P = 0.06) while 2-year incidences of nonrelapse mortality were 35% and 49% (P = 0.03), respectively. At 2-year overall survival, leukaemia-free survival and graft-versus-host disease (GVHD)-free relapse-free survival were 42% vs. 19% (P < 0.001), 40% vs. 16% (P < 0.001), and 26% vs. 12% (P = 0.002) in first CR patients versus those with advanced disease, respectively. CONCLUSIONS: We report here the first study of CBT in a large cohort of sAML patients. Main observation was that CBT rescued approximately 40% of patients with sAML in first CR.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune-mediated graft-versus-leukaemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukaemia effects after allogeneic hematopoietic cell transplantation. METHODS: Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient-year within sequential 90-day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time-dependent covariate. RESULTS: The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II-IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II-IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P < 0.001) and late (HR = 4.9, P < 0.001) mortality after UCBT. CONCLUSIONS: The occurrence of grade II-IV acute or chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft-versus-leukemia effect of GVHD.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Doença Enxerto-Hospedeiro , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Adolescente , Adulto , Idoso , Soro Antilinfocitário/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Adulto JovemRESUMO
Attractive Bose-Einstein condensates can host two types of macroscopic self-bound states: bright solitons and quantum droplets. Here, we investigate the connection between them with a Bose-Bose mixture confined in an optical waveguide. We show theoretically that, depending on atom number and interaction strength, solitons and droplets can be smoothly connected or remain distinct states coexisting only in a bistable region. We measure their spin composition, extract their density for a broad range of parameters, and map out the boundary of the region separating solitons from droplets.
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Ras-associated autoimmune leucoproliferative disorder (RALD) is a nonmalignant syndrome associated with somatic KRAS mutations. We report a patient with RALD and cutaneous lesions, the first such case reported, to our knowledge. An 8-year-old boy presented with erythematous plaques on his face and body, along with lymphadenopathies and spleen enlargement without systemic symptoms. An increased number of monocytes were found in skin biopsy, peripheral blood and bone marrow (BM). Juvenile myelomonocytic leukaemia (JMML) was suspected. Genetic study using peripheral blood showed no mutations in the KRAS, PTPN11, NRAS, CBL or BCR-ABL genes, but bone marrow analysis revealed a mutation (p-G12S/c.34 G>A) in the KRAS gene. The karyotype was normal. No KRAS mutations were found using molecular analysis of saliva. The diagnosis of RALD was proposed. The differential diagnosis between RALD and JMML is challenging because there are no established criteria to differentiate between them. The clinical course of RALD is uncertain, so long-term follow-up is recommended.
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Síndrome Linfoproliferativa Autoimune/diagnóstico , Proteínas Proto-Oncogênicas p21(ras) , Dermatopatias/etiologia , Pele/patologia , Síndrome Linfoproliferativa Autoimune/complicações , Síndrome Linfoproliferativa Autoimune/genética , Síndrome Linfoproliferativa Autoimune/patologia , Biópsia , Criança , Análise Mutacional de DNA , Diagnóstico Diferencial , Genes ras , Humanos , Leucemia Mielomonocítica Juvenil/diagnóstico , Masculino , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
The study of the factors structuring genetic variation can help to infer the neutral and adaptive processes shaping the demographic and evolutionary trajectories of natural populations. Here, we analyse the role of isolation by distance (IBD), isolation by resistance (IBR, defined by landscape composition) and isolation by environment (IBE, estimated as habitat and elevation dissimilarity) in structuring genetic variation in 25 blue tit (Cyanistes caeruleus) populations. We typed 1385 individuals at 26 microsatellite loci classified into two groups by considering whether they are located into genomic regions that are actively (TL; 12 loci) or not (NTL; 14 loci) transcribed to RNA. Population genetic differentiation was mostly detected using the panel of NTL. Landscape genetic analyses showed a pattern of IBD for all loci and the panel of NTL, but genetic differentiation estimated at TL was only explained by IBR models considering high resistance for natural vegetation and low resistance for agricultural lands. Finally, the absence for IBE suggests a lack of divergent selection pressures associated with differences in habitat and elevation. Overall, our study shows that markers located in different genomic regions can yield contrasting inferences on landscape-level patterns of realized gene flow in natural populations.
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Variação Genética , Genética Populacional , Passeriformes/genética , Animais , Evolução Biológica , Ecossistema , Fluxo Gênico , Deriva Genética , Repetições de Microssatélites , Modelos Genéticos , EspanhaRESUMO
OBJECTIVES: It is difficult to establish which patients suffering from critical lower limb ischaemia will benefit from revascularization. Risk scores can provide objectivity in decision making. The aim was to design a new risk score (ERICVA) and compare its predictive power with the PREVENT III and Finnvasc scores. METHODS: An observational retrospective study of patients who underwent revascularization (open or endovascular) in Valladolid's University Hospital between 2005 and 2010 was designed. The sample was divided into two subgroups (development and validation subsamples). After univariate analysis followed by a multivariate Cox regression, a number of variables associated with death and/or major amputation were selected, creating a weighed score called ERICVA, and a simplified version of it. The area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis was performed and the AUC of these two scores were additionally compared with the AUC of the PREVENT III and Finnvasc scales. RESULTS: Six hundred and seventy two cases with an average surveillance of 778 days were included in the study. Amputation free survival (AFS) was 84.8% at 30 days and 63.1% at 1 year. Variables associated with death and/or major amputation in the Cox regression were cerebrovascular disease, prior contralateral major amputation, diabetes mellitus, dialysis, chronic obstructive pulmonary disease, cancer, haematocrit less than 30%, neutrophil/lymphocyte ratio exceeding 5, absence of arterial Doppler signal at the ankle, emergency admission, and Rutherford stage 6; these variables were used for the ERICVA and simplified ERICVA score designs. Scores were applied to both subsamples; in the development sample the AUC of ERICVA and simplified ERICVA was significantly higher than the PREVENT III (p = .008 and p = .045) and Finnvasc (p < .0001 and p = .0013) scores; in the validation sample the AUC of ERICVA and simplified ERICVA were significantly higher than Finnvasc score (p = .0323 and p = .0017). CONCLUSIONS: The ERICVA model has a good predictive capacity for death and/or major amputation in the clinical setting, and is better than the PREVENT III and Finnvasc scores.
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Estado Terminal , Técnicas de Apoio para a Decisão , Procedimentos Endovasculares , Isquemia/terapia , Extremidade Inferior/irrigação sanguínea , Procedimentos Cirúrgicos Vasculares , Idoso , Idoso de 80 Anos ou mais , Amputação Cirúrgica , Área Sob a Curva , Comorbidade , Intervalo Livre de Doença , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Hospitais Universitários , Humanos , Isquemia/diagnóstico , Isquemia/mortalidade , Isquemia/fisiopatologia , Estimativa de Kaplan-Meier , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Seleção de Pacientes , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Espanha , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
Air pollution represents a threat to biodiversity throughout the world and particularly in the Mediterranean area, where high tropospheric ozone (O3) concentrations and atmospheric nitrogen (N) deposition are frequently recorded. Mediterranean annual pastures are among the most important ecosystems in southern Europe due to their high biodiversity and extension. Aiming to study the responses of these communities to the main atmospheric pollutants in the Mediterranean region, an experimental study was performed in an open-top chamber (OTC) facility. A mixture of six species representative of annual pastures was grown under field conditions inside the OTC. Plants were exposed for 39 days to four O3 treatments and three doses of N. The species responded heterogeneously to both factors. Legumes did not react to N but were very sensitive to O3: Trifolium species responded negatively, while Ornithopus responded positively, taking advantage of the greater sensitivity of clovers to O3. The grasses and the herb were more tolerant of O3 and grasses were the most responsive to N. Significant interactions between factors indicated a loss of effectiveness of N in O3-polluted atmospheres and an ability of O3 to counterbalance the damage induced by N input, but both effects were dependent on O3 and N levels. The inclusion of plant competition in the experimental design was necessary to reveal results that would otherwise be missed, such as the positive growth responses under elevated O3 levels. Surprisingly, competition within the legume family played the most important role in the overall response of the annual community to O3. Both tropospheric O3 and N deposition should be considered important drivers of the structure and biodiversity of Mediterranean annual pastures.
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Nitrogênio , Ozônio/farmacologia , Poluentes Atmosféricos , Poluição do Ar , Atmosfera , Ecossistema , PlantasRESUMO
The Sierra de Guadarrama mountain range, located at 60 km from Madrid City (Spain), includes high valuable ecosystems following an altitude gradient, some of them protected under the Sierra de Guadarrama National Park. The characteristic Mediterranean climatic conditions and the precursors emitted from Madrid favor a high photochemical production of ozone (O3) in the region. However, very little information is available about the patterns and levels of O3 and other air pollutants in the high elevation areas and their potential effects on vegetation. Ozone levels were monitored at three altitudes (2262, 1850, and 995 m a.s.l.) for at least 3 years within the 2005-2011 period. NO x and SO2 were also recorded at the highest and lowest altitude sites. Despite the inter-annual and seasonal variations detected in the O3 concentrations, the study revealed that SG is exposed to a chronic O3 pollution. The two high elevation sites showed high O3 levels even in winter and at nighttime, having low correlation with local meteorological variables. At the lower elevation site, O3 levels were more related with local meteorological and pollution conditions. Ozone concentrations at the three sites exceeded the thresholds for the protection of human health and vegetation according to the European Air Quality Directive (EU/50/2008) and the thresholds for vegetation protection of the CLRTAP. Ozone should be considered as a stress factor for the health of the Sierra de Guadarrama mountain ecosystems. Furthermore, since O3 levels at foothills differ from concentration in high elevation, monitoring stations in mountain ranges should be incorporated in regional air quality monitoring networks.
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Poluição do Ar/análise , Altitude , Ecossistema , Monitoramento Ambiental , Ozônio/análise , Plantas/efeitos dos fármacos , Tempo (Meteorologia) , Poluentes Atmosféricos/análise , Cidades , Humanos , Meteorologia , Estações do Ano , EspanhaRESUMO
OBJECTIVES: Fat mass ratio (FMR) has been suggested as an objective indicator of abnormal body fat distribution in HIV infection. Although it could provide more comprehensive information on body fat changes than limb fat mass, FMR has scarcely been used in clinical trials examining body fat distribution in HIV-infected patients. METHODS: A subanalysis of a controlled, randomized clinical trial in virologically suppressed HIV-1-infected men switching from zidovudine (ZDV)/lamivudine (3TC) to emtricitabine (FTC)/tenofovir (TDF) versus continuing on ZDV/3TC was carried out. FMR was assessed by dual X-ray absorptiometry (DEXA) for a period of 72 weeks. Lipoatrophy was defined as FMR ≥ 1.5. Multivariate linear regression models for the change in FMR from baseline were fitted. RESULTS: Sixty-five men were randomized and treated (28 in the FTC/TDF arm and 37 in the ZDV/3TC arm), and 57 completed the study (25 and 32 in each arm, respectively). In the FTC/TDF arm, adjusted mean FMR decreased by 0.52 at week 72 (P = 0.014), and in the ZDV/3TC arm it increased by 0.13 (P = 0.491; P between arms = 0.023). Among subjects with lipoatrophy (baseline FMR ≥ 1.5), adjusted FMR decreased by 0.76 (P = 0.003) in the FTC/TDF arm and increased by 0.21 (P = 0.411; P between arms = 0.009) in the ZDV/3TC arm. Baseline FMR and treatment group were significant predictors (P < 0.05) of post-baseline changes in FMR. CONCLUSIONS: Switching from ZDV/3TC to FTC/TDF led to an improvement in FMR, compared with progressive worsening of FMR in subjects receiving ZDV/3TC, showing that fat mass not only increased but was also distributed in a healthier way after the switch.
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Fármacos Anti-HIV/uso terapêutico , Distribuição da Gordura Corporal , Substituição de Medicamentos , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Tenofovir/uso terapêutico , Zidovudina/uso terapêutico , Absorciometria de Fóton , Adulto , Terapia Antirretroviral de Alta Atividade , Combinação de Medicamentos , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
Familial colorectal cancer type X (FCCX) encompasses a group of families with dominant inheritance pattern of colorectal cancer (CRC) but no alteration in any known CRC susceptibility gene. Therefore, the explanation of their susceptibility is a priority to offer an accurate genetic counseling. We screened the 27 coding exons and exon-intron boundaries of BRCA2 in 48 FCCX probands. We identified 29 variants including a frameshift mutation. Deleterious variant c.3847_3848delGT p.(Val1283Lysfs*2) showed cosegregation with disease as well as loss of heterozygosity (LOH) in CRC tumor DNA. This is the first evidence of germline BRCA2 pathogenic mutation associated with CRC risk. Furthermore, missense variants c.502C>A p.(Pro168Thr), c.5744C>T p.(Thr1915Met) and c.7759C>T p.(Leu2587Phe) were proposed as candidate risk alleles based on cosegregation, LOH tumor analysis and in silico testing.
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Proteína BRCA2/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Adulto , Idoso , Alelos , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Família , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Testes Genéticos , Genótipo , Mutação em Linhagem Germinativa , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Estimating the level of alpha heating and determining the onset of the burning plasma regime is essential to finding the path towards thermonuclear ignition. In a burning plasma, the alpha heating exceeds the external input energy to the plasma. Using a simple model of the implosion, it is shown that a general relation can be derived, connecting the burning plasma regime to the yield enhancement due to alpha heating and to experimentally measurable parameters such as the Lawson ignition parameter. A general alpha-heating curve is found, independent of the target and suitable to assess the performance of all laser fusion experiments whether direct or indirect drive. The onset of the burning plasma regime inside the hot spot of current implosions on the National Ignition Facility requires a fusion yield of about 50 kJ.
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Nanostructured RuOx/TiO2(110) catalysts have a remarkable catalytic activity for CO oxidation at temperatures in the range of 350-375 K. On the other hand, the RuO2(110) surface has no activity. The state-of-the-art DFT calculations indicate that the main reasons for such an impressive improvement in the catalytic activity are: (i) a decrease of the diffusion barrier of adsorbed O atoms by around 40%, from 1.07 eV in RuO2(110) to 0.66 eV in RuOx/TiO2(110), which explains the shift of the activity to lower temperatures and (ii) a lowering of the barrier by 20% for the association of adsorbed CO and O species to give CO2 (the main barrier for the CO oxidation reaction) passing from around 0.7 eV in RuO2(110) to 0.55 eV in RuOx/TiO2(110). We show that the catalytic properties of ruthenia are strongly modified when supported as nanostructures on titania, attaining higher activity at temperatures 100 K lower than that needed for pure ruthenia. As in other systems consisting of ceria nanostructures supported on titania, nanostructured ruthenia shows strongly modified properties compared to the pure oxide, consolidating the fact that the nanostructuring of oxides is a main way to attain higher catalytic activity at lower temperatures.