RESUMO
PURPOSE: There remains a need for novel therapies for patients with metastatic breast cancer (MBC). We explore the use of a novel biomarker of survival that could potentially expedite the testing of novel therapies. METHODS: We applied a tumor regression-growth model to radiographic measurement data from 393 women with MBC enrolled in PALOMA-3 examining efficacy of palbociclib in disease that had progressed on previous endocrine therapy. 261 and 132 women were randomized to fulvestrant plus palbociclib or placebo, respectively. We estimated rates of regression (d) and growth (g) of the sensitive and resistant fractions of tumors, respectively. We compared the median g of both arms. We examined the relationship between g and progression-free and overall survival (OS). RESULTS: As in other tumors, g is a biomarker of OS. In PALOMA-3, we found significant differences in g among patients with tumors sensitive to endocrine therapy but not amongst resistant tumors, emulating clinical trial results. Subgroup analysis found favorable g values in visceral metastases treated with palbociclib. Palbociclib efficacy demonstrated by slower g values was evident early in the trial, twelve weeks after the first 28 patients had been enrolled. CONCLUSION: Values of g, estimated using data collected while a patient is enrolled in a clinical trial is an excellent biomarker of OS. Our results correlate with the survival outcomes of PALOMA-3 and argue strongly for using g as a clinical trial endpoint to help inform go/no-go decisions, improve trial efficiency, and deliver novel therapies to patients sooner.
Assuntos
Neoplasias da Mama , Piridinas , Feminino , Humanos , Biomarcadores , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Piperazinas , Piridinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2RESUMO
Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.
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Cuidados Críticos , Obtenção de Tecidos e Órgãos , Humanos , Estudos Prospectivos , Masculino , Feminino , Obtenção de Tecidos e Órgãos/métodos , Pessoa de Meia-Idade , Idoso , Espanha , Adulto , Lesões Encefálicas , Morte Encefálica , Unidades de Terapia IntensivaRESUMO
The widespread use of low or medium pressure mercury lamps in UV-C water disinfection should consider recent advances in UV-C LED lamps that offer a more sustainable approach and avoid its main drawbacks. The type of water and the mode of operation are critical when deciding on the treatment technology to be used. Therefore, this study investigates the potential application of UV-C LED disinfection technology in terms of kinetics, environmental assessment, and economic analysis for two scenarios: the continuous disinfection of a wastewater treatment plant (WWTP), and disinfection of harvested rainwater (RWH) in a residential household that operates intermittently. Experiments are conducted using both the new UV-C LED system and the conventional mercury lamp to disinfect real wastewater. Removal of total coliforms and Escherichia coli bacteria, with concentrations of approximately 105 and 104 CFU per 100 mL has been followed to assess the performance of both types of UV-C lamps. The experimental study provides kinetic parameters that have been further used in the environmental assessment conducted from a life cycle perspective. Additionally, considering the significant role of electricity consumption, a preliminary economic analysis has been conducted. The results indicate that first-order kinetic constants of pathogens removal with UV-C LEDs achieve 1.4 times higher values than Hg lamp. Regarding the environmental and economic assessment, for disinfection systems operating continuously, LEDs result in environmental impacts 5 times higher than Hg lamp in most categories, indicating that Hg lamps offer a viable option both from economic and environmental point of view. However, for installations with intermittent operation, LEDs emerge as the most competitive alternative, due to their ability to be turned on and off without affecting their lifespan. This study shows that UV-C LED lamps hold promise to replace conventional mercury lamps in a near future.
Assuntos
Desinfecção , Raios Ultravioleta , Purificação da Água , Desinfecção/métodos , Purificação da Água/métodos , Purificação da Água/economia , Escherichia coli/efeitos da radiação , Águas ResiduáriasRESUMO
To evaluate the prevalence of transmitted drug resistance (TDR) to nucleoside and nonnucleoside reverse transcriptase inhibitors (NRTI, NNRTI), protease inhibitors (PI), and integrase strand transfer inhibitors (INSTI) in Spain during the period 2019-2021, as well as to evaluate transmitted clinically relevant resistance (TCRR) to antiretroviral drugs. Reverse transcriptase (RT), protease (Pro), and Integrase (IN) sequences from 1824 PLWH (people living with HIV) were studied. To evaluate TDR we investigated the prevalence of surveillance drug resistance mutations (SDRM). To evaluate TCRR (any resistance level ≥ 3), and for HIV subtyping we used the Stanford v.9.4.1 HIVDB Algorithm and an in-depth phylogenetic analysis. The prevalence of NRTI SDRMs was 3.8% (95% CI, 2.8%-4.6%), 6.1% (95% CI, 5.0%-7.3%) for NNRTI, 0.9% (95% CI, 0.5%-1.4%) for PI, and 0.2% (95% CI, 0.0%-0.9%) for INSTI. The prevalence of TCRR to NRTI was 2.1% (95% CI, 1.5%-2.9%), 11.8% for NNRTI, (95% CI, 10.3%-13.5%), 0.2% (95% CI, 0.1%-0.6%) for PI, and 2.5% (95% CI, 1.5%-4.1%) for INSTI. Most of the patients were infected by subtype B (79.8%), while the majority of non-Bs were CRF02_AG (n = 109, 6%). The prevalence of INSTI and PI resistance in Spain during the period 2019-2021 is low, while NRTI resistance is moderate, and NNRTI resistance is the highest. Our results support the use of integrase inhibitors as first-line treatment in Spain. Our findings highlight the importance of ongoing surveillance of TDR to antiretroviral drugs in PLWH particularly with regard to first-line antiretroviral therapy.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Espanha/epidemiologia , Filogenia , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/farmacologia , Antirretrovirais/uso terapêutico , Integrases/genética , Integrases/uso terapêutico , Mutação , Farmacorresistência Viral/genética , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , PrevalênciaRESUMO
Acidiphilium cryptum is an acidophilic, heterotrophic, and metallotolerant bacteria able to use dissolved oxygen or Fe(III) as an electron sink. The ability of this extremophile to accumulate poly(3-hydroxybutyrate) (PHB) and secrete extracellular polymeric substances (EPS) has also been reported. Hence, the aim of this work is to characterize the production of PHB and EPS by the wild strain DSM2389 using glycerol in shaken flasks and bioreactor. Results showed that maximum PHB accumulation (37-42% w/w) was obtained using glycerol concentrations of 9 and 15 g L-1, where maximum dry cell weight titers reached 3.6 and 3.9 g L-1, respectively. The culture in the bioreactor showed that PHB accumulation takes place under oxygen limitation, while the redox potential of the culture medium could be used for online monitoring of the PHB production. Recovered EPS was analyzed by Fourier-transform infrared spectroscopy and subjected to gas chromatography-mass spectrometry after cleavage and derivatization steps. These analyses showed the presence of sugars which were identified as mannose, rhamnose and glucose, in a proportion near to 3.2:2.3:1, respectively. Since glycerol had not been used in previous works, these findings suggest the potential of A. cryptum to produce biopolymers from this compound at a large scale with a low risk of microbial contamination due to the low pH of the fermentation process.
Assuntos
Matriz Extracelular de Substâncias Poliméricas , Glicerol , Ácido 3-Hidroxibutírico , Compostos Férricos , PoliésteresRESUMO
A cross-sectional survey to assess the prevalence of Enterobius vermicularis infection and its associated factors among the child population of infant, preschool and school age in the urban, rural and indigenous population of Iguazú city, in subtropical Argentina was presented. Additionally, the status of enterobiasis at country level was reviewed and analysed. Enterobius vermicularis presence was assessed employing an oviscopic serial sampling technique. Statistical analysis of socio-demographic determinants was performed by generalized linear mixed models at individual, household and community levels. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used to gather national information about E. vermicularis prevalence spanning the decade 20102020. A total of 916 children from 470 families participated. Overall prevalence was 29.8%, with 25.3, 30.7 and 34.2% detected for children inhabiting urban, rural and indigenous villages, respectively. The multi-level analysis showed that the presence of E. vermicularis was mostly determined by individual (e.g. age, playing habits, previous pinworm infection) and household-level factors (e.g. family size, overcrowding conditions). Interestingly, WASH variables, such as waste disposal, analysed at community level were also important. Data were analysed to provide eco-epidemiological features of enterobiasis in a heterogeneous subtropical child population in the same territory but with different socio-sanitary realities. The importance of promoting multi-level actions against the determinants identified, to control this public health problem integratively was evidenced. The scoping review of national data updated the state of knowledge of this parasitosis, identifying risk determinants and gaps in knowledge at country level.
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Enterobíase , Animais , Argentina/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Enterobíase/epidemiologia , Enterobius , Humanos , Lactente , Prevalência , Fatores de RiscoRESUMO
Neural stem cells continuously generate newborn neurons that integrate into and modify neural circuitry in the adult hippocampus. The molecular mechanisms that regulate or perturb neural stem cell proliferation and differentiation, however, remain poorly understood. Here, we have found that mouse hippocampal radial glia-like (RGL) neural stem cells express the synaptic cochaperone cysteine string protein-α (CSP-α). Remarkably, in CSP-α knockout mice, RGL stem cells lose quiescence postnatally and enter into a high-proliferation regime that increases the production of neural intermediate progenitor cells, thereby exhausting the hippocampal neural stem cell pool. In cell culture, stem cells in hippocampal neurospheres display alterations in proliferation for which hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway is the primary cause of neurogenesis deregulation in the absence of CSP-α. In addition, RGL cells lose quiescence upon specific conditional targeting of CSP-α in adult neural stem cells. Our findings demonstrate an unanticipated cell-autonomic and circuit-independent disruption of postnatal neurogenesis in the absence of CSP-α and highlight a direct or indirect CSP-α/mTOR signaling interaction that may underlie molecular mechanisms of brain dysfunction and neurodegeneration.
Assuntos
Proteínas de Choque Térmico HSP40 , Proteínas de Membrana , Células-Tronco Neurais/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Células Cultivadas , Proteínas de Choque Térmico HSP40/genética , Proteínas de Choque Térmico HSP40/metabolismo , Hipocampo/citologia , Lisossomos/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Neurogênese/genética , Lipofuscinoses Ceroides Neuronais , Transdução de Sinais/genéticaRESUMO
BACKGROUND: In 2012, the central government of Spain enacted Royal Decree-Law (RDL) 16/2012 and Royal Decree (RD) 1192/2012, which abolished universal healthcare coverage, thus limiting access to care for undocumented immigrants. Free health care was also no longer granted to anyone who has never been employed. In this context, this study investigated the prevalence of late HIV diagnoses (LHDs) among immigrants living in Spain vs. native-born Spaniards. METHODS: Data (n = 5943) from the 2010 to 2015 Cohort of the Spanish AIDs Research Network were used, including HIV-positive and antiretroviral therapy (ART)-naïve patients throughout Spain. Multivariate logistic models were fitted to compare the prevalence of LHD among the groups, adjusting for covariates. RESULTS: The prevalence of LHD in the total sample was 39.5%. Compared with native-born Spaniards (n = 4445), immigrants (n = 1488) were more likely to have LHD (37.4% vs. 45.7%, respectively; P < 0.001). Multivariate analysis showed that the prevalence ratio of LHD among immigrants vs. native-born Spaniards was 1.15 [95% confidence interval (CI), 1.02-1.28], after adjusting for covariates. This disparity widened from 2010 to 2011 (APR = 1.14, 95% CI, 1.02-1.29) to 2012-15 (APR = 1.28, 95% CI, 1.17-1.39), although the change was not statistically significant. CONCLUSIONS: Immigrants in Spain had a higher risk of LHD compared with native-born counterparts. LHD is an important healthcare marker due to the positive benefits of early HIV diagnosis, including prevention, improvements in health outcomes and decreases in overall cost of treatment. More research is needed on the causes of the disparity and potential social and policy interventions to reduce the prevalence of LHD among immigrants.
Assuntos
Emigrantes e Imigrantes , Infecções por HIV , Imigrantes Indocumentados , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Humanos , Povos Indígenas , Espanha/epidemiologiaRESUMO
OBJECTIVES: We report the results of the reverse transcriptase (RT)/protease (PR) transmitted drug resistance (TDR) prevalence study in 2018, focusing on doravirine resistance-associated mutations and the differences observed when Stanford or French National Agency for AIDS Research (ANRS)/Spanish Network of AIDS Research (RIS)/IAS-USA resistance interpretation algorithms are used to describe clinically relevant resistance. METHODS: We used the WHO 2009 list to investigate the prevalence of NNRTI, NRTI and PI TDR, in treatment-naive HIV-1-infected patients, adding mutations E138A/G/K/Q/R, V106I, V108I, V179L, G190Q, H221Y, F227C/L/V, M230IDR, L234I, P236L and Y318F in RT. The prevalence of doravirine resistance-associated mutations, as described by Soulie et al. in 2019, was evaluated. Clinically relevant TDR was investigated using the latest versions of ANRS, RIS, IAS-USA and Stanford algorithms. RESULTS: NNRTI mutations were detected in 82 of 606 (13.5%) patients. We found 18 patients (3.0%) with NRTI mutations and 5 patients (0.8%) with PI mutations. We detected 11 patients harbouring doravirine resistance-associated mutations (prevalence of 1.8%). Furthermore, we observed important differences in clinically relevant resistance to doravirine when ANRS/RIS (0.7%), IAS-USA (0.5%) or Stanford algorithms (5.0%) were used. V106I, which was detected in 3.8% of the patients, was the main mutation driving these differences. V106I detection was not associated with any of the clinical, demographic or virological characteristics of the patients. CONCLUSIONS: The prevalence of NRTI and PI TDR remains constant in Spain. Doravirine TDR is very infrequent by RIS/ANRS/IAS-USA algorithms, in contrast with results using the Stanford algorithm. Further genotype-phenotype studies are necessary to elucidate the role of V106I in doravirine resistance.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Algoritmos , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Mutação , Prevalência , Piridonas , Espanha , TriazóisRESUMO
OBJECTIVE: To estimate trends in the prevalence of child stunting in the population of children under 5 years of age covered by public health programmes, between 2009 and 2014 in Misiones, Argentina. METHODS: Using Bayesian model-based geostatistics, we evaluated 724 872 anthropometric measurements corresponding to 110 633 children. In order to identify disparities at local scale, we evaluated the hypotheses of a differential reduction of stunting according to the geographical location (at two-level spatial resolution) and to the socioeconomic level in a rural or urban environment. RESULTS: The prevalence of stunting had fallen significantly in the province overall. Sex and age defined gender disparities at individual level, and there were regional disparities with higher prevalence values in the north and northeast regions. In these areas, stunting decreased to a greater degree during the studied period, although the spatial pattern remained smoother. Stunting increased in peripheral urban and dispersed rural areas that are socioeconomically vulnerable. CONCLUSIONS: The spatial multi-level geostatistical estimates of child undernutrition provide a precision public health tool to target public policies to those populations with the greatest need, in order to reduce health disparities.
OBJECTIF: Estimer les tendances dans la prévalence du retard de croissance dans la population des enfants de moins de 5 ans couverts par les programmes de santé publique, entre 2009 et 2014 à Misiones, en Argentine. MÉTHODES: En utilisant la géostatistique basée sur un modèle bayésien, nous avons évalué 724.872 mesures anthropométriques correspondant à 110.633 enfants. Afin d'identifier les disparités à l'échelle locale, nous avons évalué les hypothèses d'une réduction différentielle du retard de croissance en fonction de la situation géographique (à une résolution spatiale à deux niveaux) et du niveau socioéconomique en milieu rural ou urbain. RÉSULTATS: La prévalence du retard de croissance avait considérablement diminué dans l'ensemble de la province. Le sexe et l'âge définissaient des disparités entre les sexes au niveau individuel, et il y avait des disparités régionales avec des valeurs de prévalence plus élevées dans les régions du nord et du nord-est. Dans ces régions, le retard de croissance a diminué plus fortement au cours de la période étudiée, bien que le modèle spatial soit resté plus lisse. Le retard de croissance a augmenté dans les zones urbaines périphériques et les zones rurales dispersées qui sont socioéconomiquement vulnérables. CONCLUSIONS: Les estimations géostatistiques spatiales à plusieurs niveaux de la sous-nutrition infantile fournissent un outil de santé publique de précision pour cibler les politiques publiques sur les populations qui en ont le plus besoin, afin de réduire les disparités en matière de santé.
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Transtornos do Crescimento/epidemiologia , Fatores Socioeconômicos , Fatores Etários , Argentina/epidemiologia , Teorema de Bayes , Pré-Escolar , Feminino , Geografia , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Masculino , Estado Nutricional , Prevalência , População Rural/estatística & dados numéricos , Fatores Sexuais , População Urbana/estatística & dados numéricosRESUMO
Giardia is a parasite distributed worldwide and one of the most prevalent intestinal protozoa in Argentina. We analysed all the national information regarding the prevalence of Giardia infections in humans, animals and environmental surveys over the last 40 years. In this work, we used Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and the period between 1980 and 2019 was defined as time lapse for inclusion of the studies. The analysis was conducted using the LILACS, PubMed, Scopus and Argentina SciELO databases employing as keywords 'Giardia' AND 'Argentina'. We also carried out a manual review of papers. Of 304 articles, 92 fitted the eligibility criteria. Giardia was reported in 15 of the 23 Argentine provinces; human prevalence was between 3.4 and 64.8%. Indigenous children and residents in peri-urban areas had the higher infection rates. In animals, Giardia was identified mainly in dogs with a prevalence of 8.9 ± 7.0%, and studies of wild animals and cattle were notably scarce. Environmental studies showed that Giardia was detected in the soil and water which may act as reservoirs for this parasite revealing the need to modify the national water treatment legislation. The identification of Giardia genetic assemblages in the studies analysed was limited and showed that genotypes AII and B were found in humans while assemblage B was mainly detected in animals. This report provides useful information on epidemiological aspects of giardiasis in Argentina that may help to define future research priorities and provides useful tools for professionals regarding actual information on the prevalence of this infection.
Assuntos
Água Potável/parasitologia , Giardia lamblia/genética , Giardia lamblia/isolamento & purificação , Giardíase/epidemiologia , Solo/parasitologia , Adolescente , Animais , Animais Selvagens/parasitologia , Argentina/epidemiologia , Bovinos , Criança , Pré-Escolar , Cães , Fezes/parasitologia , Feminino , Genótipo , Humanos , Povos Indígenas/estatística & dados numéricos , Prevalência , Fatores de Risco , Inquéritos e Questionários , Purificação da ÁguaRESUMO
BACKGROUND: Cellulosimicrobium species, formely known as Oerskovia species, are gram-positive bacilli belonging to the order Actinomycetales. They rarely cause human infections. The genus comprises two pathogenic species in humans: C. cellulans and C. funkei. Based on a case report, we provide a review of the literature of infections caused by Cellulosimicrobium/Oerskovia, in order to improve our knowledge of this unusual infection. CASE PRESENTATION: An 82-year-old woman with aortic prosthetic valve presented to the hospital with fever and heart failure. Further work up revealed the diagnosis of C. cellulans infective endocarditis (IE). The strain was identified by MALDI-TOF MS, API Coryne and 16S rRNA sequencing. The patient was deemed not to be an operative candidate and died despite the antibiotic therapy 35 days after admission. CONCLUSIONS: Reviewing cases of Cellulosimicrobium species infections and communicating the successful and unsuccessful clinical experiences can assist future healthcare providers. Our case and those previously reported indicate that Cellulosimicrobium species usually infect immunocompromised patients or foreign body carriers. The most frequent pattern of infection is central venous catheter related bacteremia. The optimal treatment should include foreign body removal and valve surgery should be considered in case of IE.
Assuntos
Infecções por Actinomycetales/diagnóstico , Actinomycetales/isolamento & purificação , Actinomycetales/efeitos dos fármacos , Actinomycetales/genética , Infecções por Actinomycetales/complicações , Infecções por Actinomycetales/tratamento farmacológico , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/tratamento farmacológico , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Humanos , Testes de Sensibilidade Microbiana , RNA Ribossômico 16S/química , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
PURPOSE: Because the currently available questionnaires to evaluate sexual changes on breast cancer women only address the sexual sphere with a few questions our purpose was to develop a questionnaire that assesses changes in sexual dysfunction and satisfaction in women treated for breast cancer. METHODS: A sample was selected of women aged between 18 and 65 who had had surgery for breast cancer, completed neoadjuvant/adjuvant chemotherapy treatment and could be receiving adjuvant hormonal treatment, with an active sex life at least 3 months before starting treatment. Metastatic disease was excluded. A questionnaire structured in 4 dimensions was developed. The MOS SF-12 and QLQ-BR23 questionnaires were also provided. The following metric properties were evaluated: item analysis; internal consistency; temporal stability; construct validity; concurrent, convergent and divergent validity; and feasibility. RESULTS: Three samples were recruited: a pilot sample of 20; a reduction sample of 152; and a validation sample of 148. The presence of 6 dimensions was confirmed: 1) Loss of sex drive; 2) worsening of body image; 3) psychological coping; 4) discomfort during intercourse; 5) satisfaction with sexual relations; and 6) satisfaction with breast reconstruction. Good goodness-of-fit statistics were obtained (χ2/df = 1.5, GFI = 0.9, AGFI = 0.84, CFI = 0.959, RMSEA = 0.062). Reliability was good (α = 0.855), as was test-retest stability (r = 0.838). The correlation with the convergent questionnaires proved to be higher than that obtained with generic measurements. CONCLUSIONS: We were able to develop a short questionnaire (17 items) capable of measuring sexual satisfaction in women with breast cancer with good metric properties.
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Neoplasias da Mama/psicologia , Orgasmo , Qualidade de Vida , Inquéritos e Questionários/normas , Adaptação Psicológica , Adulto , Idoso , Imagem Corporal/psicologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
This work reports the comparative performance of two Advanced Oxidation Processes (AOPs), electrochemical oxidation and photocatalysis, as individual technological alternatives for the treatment of effluents containing p-cresol. First, the influence of operating parameters in the oxidation and mineralization yield was carried out together with kinetic analysis. Boron Doped Diamond (BDD), RuO2 and Pt as anodic materials, Na2SO4 and NaCl as supporting electrolytes and different current densities were evaluated in electrochemical oxidation whereas the effect of TiO2 concentration and radiation was studied in the photocatalytic degradation. Then, the parameter Electrical Energy per Order (EEO) was calculated to compare the energy consumption in both AOPs, concluding that under the studied conditions the electrochemical treatment with BDD, Na2SO4 and 125 A m-2 showed the best energy efficiency, with an EEO of 5.83 kW h m-3 order-1 for p-cresol and 58.05 kW h m-3 order-1 for DOC removal, respectively.
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Boro , Diamante , Eletrodos , Cinética , OxirreduçãoRESUMO
In Gram-negative bacteria, tyrosine phosphorylation has been shown to play a role in the control of exopolysaccharide (EPS) production. This study demonstrated that the chromosomal ORF SMc02309 from Sinorhizobium meliloti 2011 encodes a protein with significant sequence similarity to low molecular mass protein-tyrosine phosphatases (LMW-PTPs), such as the Escherichia coli Wzb. Unlike other well-characterized EPS biosynthesis gene clusters, which contain neighbouring LMW-PTPs and kinase, the S. meliloti succinoglycan (EPS I) gene cluster located on megaplasmid pSymB does not encode a phosphatase. Biochemical assays revealed that the SMc02309 protein hydrolyses p-nitrophenyl phosphate (p-NPP) with kinetic parameters similar to other bacterial LMW-PTPs. Furthermore, we show evidence that SMc02309 is not the LMW-PTP of the bacterial tyrosine-kinase (BY-kinase) ExoP. Nevertheless, ExoN, a UDP-glucose pyrophosphorylase involved in the first stages of EPS I biosynthesis, is phosphorylated at tyrosine residues and constitutes an endogenous substrate of the SMc02309 protein. Additionally, we show that the UDP-glucose pyrophosphorylase activity is modulated by SMc02309-mediated tyrosine dephosphorylation. Moreover, a mutation in the SMc02309 gene decreases EPS I production and delays nodulation on Medicago sativa roots.
Assuntos
Polissacarídeos Bacterianos/biossíntese , Proteínas Tirosina Fosfatases/metabolismo , Sinorhizobium meliloti/enzimologia , Sinorhizobium meliloti/metabolismo , UTP-Glucose-1-Fosfato Uridililtransferase/metabolismo , Medicago sativa/microbiologia , Nodulação , Raízes de Plantas/microbiologiaRESUMO
SUMOylation, a posttranslational modification of proteins, has been recently described as vital in eukaryotic cells. In a previous work, we analyzed the role of SUMO protein and the genes encoding the putative enzymes of the SUMOylation pathway in the parasite Giardia lamblia. Although we observed several SUMOylated proteins, only the enzyme Arginine Deiminase (ADI) was confirmed as a SUMOylated substrate. ADI is involved in the survival of the parasite and, besides its role in ATP production, it also catalyzes the modification of arginine residues to citrulline in the cytoplasmic tail of surface proteins. During encystation, however, ADI translocates to the nuclei and downregulates the expression of the Cyst Wall Protein 2 (CWP2). In this work, we made site-specific mutation of the ADI SUMOylation site (Lys101) and observed that transgenic trophozoites did not translocate to the nuclei at the first steps of encystation but shuttled in the nuclei late during this process through classic nuclear localization signals. Inside the nuclei, ADI acts as a peptidyl arginine deiminase, being probably involved in the downregulation of CWPs expression and cyst wall formation. Our results strongly indicate that ADI plays a regulatory role during encystation in which posttranslational modifications of proteins are key players.
Assuntos
Epigênese Genética , Giardia lamblia/genética , Giardia lamblia/metabolismo , Iminas/metabolismo , Proteínas de Protozoários/metabolismo , Esporos de Protozoários/metabolismo , Sumoilação , Sequência de Aminoácidos , Animais , Núcleo Celular/enzimologia , Simulação por Computador , Regulação para Baixo , Giardia lamblia/enzimologia , Hidrolases/química , Hidrolases/metabolismo , Lisina/metabolismo , Modelos Biológicos , Dados de Sequência Molecular , Sinais de Localização Nuclear , Processamento de Proteína Pós-Traducional , Transporte Proteico , Desiminases de Arginina em ProteínasRESUMO
The current consensus is that plant responses to canopy shade involve the perception of low red to far-red ratios (R:FRs) by phytochrome B (phyB), which leads to the direct activation of auxin synthesis genes by PHYTOCHROME INTERACTING FACTORs (PIFs). In addition to its effect on R:FRs, shade also reduces irradiance, but whether shade-induced drops in irradiance affect phyB activity has not been demonstrated. To address this issue, we investigated whether irradiance and R:FRs have similar effects on the nuclear distribution of phyB in petiole cells of light-grown plants. Under high-irradiance white light, phyB formed large nuclear bodies. Lowering irradiance without changing R:FRs or lowering R:FRs by adding far-red light led to the appearance of small nuclear bodies containing phyB. Large nuclear bodies remained but with some concomitant reduction in diameter. The appearance of small nuclear bodies was rapid, stable, and reversible upon the return to high irradiance and high R:FRs. High levels of red light but not of blue light were enough to restrain the formation of small phyB nuclear bodies. Irradiance was effective within the range found in natural canopies and even under relatively low R:FRs. The promotion of leaf hyponasty by lowering irradiance was impaired in phyB and pif mutants, as previously reported for the response to R:FRs. The expression of auxin-related genes showed a similar hierarchy of response to low R:FRs and low irradiance. We propose that phyB is able to perceive not only the low R:FRs, but also the low irradiance of shade.
RESUMO
This paper reports the first finding of Diphyllobothrium sp. eggs in Canis familiaris (domestic dog) from Puerto Iguazú, a subtropical city of Misiones province, Argentina. In 2013, two positive cases of Diphyllobothrium sp. eggs were detected during an annual parasitological survey of dogs. Dog feces were collected in vials containing 10% formalin and processed using Telemann's sedimentation and Sheather's flotation techniques. The two cases were detected in rural areas of the municipality. Since Misiones is not a part of the endemic area of diphyllobothriasis and given the fact that it is located in the three-border area of Argentina, Brazil and Paraguay, we consider this finding of great importance to public health. We stress the need for updating the current knowledge about the life cycle of these parasites considering the range of intermediate and definitive hosts, their zoonotic potential, and the epidemiological situation in non-endemic areas.
Assuntos
Difilobotríase/veterinária , Diphyllobothrium/isolamento & purificação , Doenças do Cão/epidemiologia , Ração Animal/parasitologia , Animais , Argentina/epidemiologia , Clima , Estudos Transversais , Difilobotríase/epidemiologia , Difilobotríase/parasitologia , Reservatórios de Doenças , Doenças do Cão/parasitologia , Cães/parasitologia , Fezes/parasitologia , Peixes/parasitologia , Parasitologia de Alimentos , Humanos , Óvulo/ultraestrutura , Saúde Pública , Viagem , Água/parasitologia , Poluição da Água , ZoonosesRESUMO
This work studies the photocatalytic degradation of solutions containing 0.11 mM of a glucocorticoid (dexamethasone, DEX) and 0.11 mM of an herbicide (S-metolachlor, MTLC), organohalogenated compounds containing fluorine and chlorine atoms in their molecules, respectively. To treat 1 L volume, a mass of 0.5 g of TiO2/rGO composite in suspension has been used as photocatalyst, irradiated with UV-A LEDs with 200 W m-2 of irradiance. MTLC is partially adsorbed on the surface of the catalyst, while DEX is not adsorbed, showing different degradation kinetics. The halogen ions released into the solution from the breakage of the parent molecules, F- and Cl- respectively, were analysed. In the case of MTLC, the released Cl- followed two different kinetic trends, being faster, and with a rate that matched the rate of MTLC disappearance, the part corresponding to non-adsorbed MTLC. In the experiments with DEX solutions a different behaviour was observed; the released F- in the photocatalytic degradation was partially adsorbed on the catalyst surface, but the adsorption capacity decreased with the use of the photocatalyst in consecutive cycles until the solubilised F- matched the degraded concentration of DEX. Furthermore, the mass balance between the degraded contaminant and the solubilised halogen anion, for both contaminants, allowed to conclude the absence of halogenated intermediates under the final operating conditions, that is a remarkable outcome in water remediation processes.
Assuntos
Poluentes Ambientais , Fotólise , Halogênios , Dexametasona , Titânio , CatáliseRESUMO
During the COVID-19 pandemic, bioethical concerns were raised and there was even a â³resurgence of bioethics. â³ In this work, we review the scientific articles published by Spanish authors in relation to bioethical issues in the three years following the declaration of the pandemic. Seventy publications have been selected. Of all of them, the topic that lent itself to the most debate was that of prioritization in the use of health resources. A consensus was reached that ruled out that age could be considered as a sole exclusion criterion in healthcare or in a possible admission to the ICU. And the importance of taking special care of the most vulnerable and adapting care to the conditions of each patient without excluding anyone was recalled. Other relevant topics were the contrast between autonomy and the common good, the immune passport, vaccination, rigor in research and the publication of results, the professionalism of health personnel, misinformation, care for nursing homes, telemedicine, and the importance of the exercise of virtues. After the experience of both vulnerability and the need to exercise solidarity, many works raise the desire and the possibility of being able to overcome the pandemic being better.