Fotodegradação de esparfloxacino e isolamento de seus produtos de degradação utilizando CLAE

Sparfloxacin, a third generation fluoroquinolone derivative,is a potent antibacterial agent active against a wide range ofGram-positive and Gram-negative organisms including Streptococcus pneumoniae, Staphylococcus aureus, methicillinresistant S. aureus, Legionella spp., Mycoplasma spp.,Chlamydia spp. and Mycobacterium spp. A drawback offluoroquinolones is their photoreactivity. Sparfloxacin hasbeen studied in terms of therapeutic activities. However, the reare few published of analytical methods being applied tosparfloxacin. The aim in this study was to determine the photodegradation products of sparfloxacin, when submittedto UV light, and to characterize two of these products,designated SPAX-PDP1 and SPAX-PDP2. An acceleratedstudy of stability in methanol solution was carried out byexposing a solution of sparfloxacin to UV light (peakwavelength 290 nm) for 36 hours at room temperature. Theproducts were analyzed by NMR spectrophotometry, IR spectrometry and mass spectrophotometry. The result ssuggest that the products isolated here could be used toestimate the degradation of sparfloxacin in a stability study. However, the low activity exhibited by UV-irradiated sparfloxacin is a source of concern that demands further investigation of the mechanism of its photodegradation mechanism.Esparfloxacino, fluorquinolona de terceira geração, é umpotente agente antibacteriano ativo contra Gram-positivos eGram-negativos, incluindo Streptococcus pneumoniae,Staphylococcus aureus, S. aureus meticilina resistentes,Legionella spp., Mycoplasma spp., Chlamydia spp. eMycobacterium spp. Um aspecto importante dasfluorquinolonas é sua fotoinstabilidade. O esparfloxacino temsido amplamente estudado em termos de atividadesterapêuticas. Entretanto, poucos relatos a respeito de métodosanalíticos para esta quinolona são disponíveis na literatura. O objetivo deste trabalho foi determinar a fotoestabilidadede esparfloxacino submetido à luz UV, bem como caracterizar dois produtos, codificados como SPAX-PDP1 e SPAX-PDP2. Um estudo acelerado de estabilidade foi realizado submetendo-se o esparfloxacino a luz UV (comprimento de onda 290 nm) durante 36 horas em temperatura ambiente. Os resultados foram analisados por espectrofotômetro de massas, de RMN de 1H e de 13C e espectrometria na região de infravermelho. Os resultados sugerem que os produtos isolados podem ser usados para determinar a degradação de esparfloxacino em estudos de fotoestabilidade. No entanto, abaixa atividade do esparfloxacino submetido à luz UV demonstra a necessidade de investigações a respeito do mecanismo de fotodegradação deste fármaco

Reef response to sea-level and environmental changes during the last deglaciation: Integrated Ocean Drilling Program Expedition 310, Tahiti Sea Level

The last deglaciation is characterized by a rapid sea-level rise and coeval abrupt environmental changes. The Barbados coral reef record suggests that this period has been punctuated by two brief intervals of accelerated melting (meltwater pulses, MWP), occurring at 14.08-13.61 ka and 11.4-11.1 ka (calendar years before present), that are superimposed on a smooth and continuous rise of sea level. Although their timing, magnitude, and even existence have been debated, those catastrophic sea-level rises are thought to have induced distinct reef drowning events. The reef response to sea-level and environmental changes during the last deglacial sea-level rise at Tahiti is reconstructed based on a chronological, sedimentological, and paleobiological study of cores drilled through the relict reef features on the modern forereef slopes during the Integrated Ocean Drilling Program Expedition 310, complemented by results on previous cores drilled through the Papeete reef. Reefs accreted continuously between 16 and 10 ka, mostly through aggradational processes, at growth rates averaging 10 mm yr-1. No cessation of reef growth, even temporary, has been evidenced during this period at Tahiti. Changes in the composition of coralgal assemblages coincide with abrupt variations in reef growth rates and characterize the response of the upward-growing reef pile to nonmonotonous sea-level rise and coeval environmental changes. The sea-level jump during MWP 1A, 16 ± 2 m of magnitude in ~350 yr, induced the retrogradation of shallow-water coral assemblages, gradual deepening, and incipient reef drowning. The Tahiti reef record does not support the occurrence of an abrupt reef drowning event coinciding with a sea-level pulse of ~15 m, and implies an apparent rise of 40 mm yr-1 during the time interval corresponding to MWP 1B at Barbados. © 2012 Geological Society of America

Correlations equalities and some upper bounds for the critical temperature for spin one systems

Starting from correlation identities for the Blume-Capel spin 1 systems and using correlation inequalities, we obtain rigorous upper bounds for the critical temperature.The obtained results improve over effective field type results.Comment: 13 page

Targeted massively parallel sequencing panel to diagnose genetic endocrine disorders in a tertiary hospital

Objectives: To analyze the efficiency of a multigenic targeted massively parallel sequencing panel related to endocrine disorders for molecular diagnosis of patients assisted in a tertiary hospital involved in the training of medical faculty. Material and methods: Retrospective analysis of the clinical diagnosis and genotype obtained from 272 patients in the Endocrine unit of a tertiary hospital was performed using a custom panel designed with 653 genes, most of them already associated with the phenotype (OMIM) and some candidate genes that englobes developmental, metabolic and adrenal diseases. The enriched DNA libraries were sequenced in NextSeq 500. Variants found were then classified according to ACMG/AMP criteria, with Varsome and InterVar. Results: Three runs were performed; the mean coverage depth of the targeted regions in panel sequencing data was 249×, with at least 96.3% of the sequenced bases being covered more than 20-fold. The authors identified 66 LP/P variants (24%) and 27 VUS (10%). Considering the solved cases, 49 have developmental diseases, 12 have metabolic and 5 have adrenal diseases. Conclusion: The application of a multigenic panel aids the training of medical faculty in an academic hospital by showing the picture of the molecular pathways behind each disorder. This may be particularly helpful in developmental disease cases. A precise genetic etiology provides an improvement in understanding the disease, guides decisions about prevention or treatment, and allows genetic counseling

The Dark Sides of Social Policy: From Neoliberalism to Resurgent Right-wing Populism

This Forum Debate explores the confluence of neoliberal, populist, conservative and reactionary influences on contemporary ideologies and practices of social policy, with a focus on the poorer peripheries of global

The economic impact of two diagnostic strategies in the management of restorations in primary teeth : a health economic analysis plan for a trial-based economic evaluation

Background Different approaches have been used by dentists to base their decision. Among them, there are the aesthetical issues that may lead to more interventionist approaches. Indeed, using a more interventionist strategy (the World Dental Federation - FDI), more replacements tend to be indicated than using a minimally invasive one (based on the Caries Around Restorations and Sealants—CARS). Since the resources related to the long-term health effects of these strategies have not been explored, the economic impact of using the less-invasive strategy is still uncertain. Thus, this health economic analysis plan aims to describe methodologic approaches for conducting a trial-based economic evaluation that aims to assess whether a minimally invasive strategy is more efficient in allocating resources than the conventional strategy for managing restorations in primary teeth and extrapolating these findings to a longer time horizon. Methods A trial-based economic evaluation will be conducted, including three cost-effectiveness analyses (CEA) and one cost-utility analysis (CUA). These analyses will be based on the main trial (CARDEC-03/NCT03520309), in which children aged 3 to 10 were included and randomized to one of the diagnostic strategies (based on FDI or CARS). An examiner will assess children’s restorations using the randomized strategy, and treatment will be recommended according to the same criteria. The time horizon for this study is 2 years, and we will adopt the societal perspective. The average costs per child for 24 months will be calculated. Three different cost-effectiveness analyses (CEA) will be performed. For CEAs, the effects will be the number of operative interventions (primary CEA analysis), the time to these new interventions, the percentage of patients who did not need new interventions in the follow-up, and changes in children’s oral health-related quality of life (secondary analyses). For CUA, the effect will be tooth-related quality-adjusted life years (QALYs). Intention-to-treat analyses will be conducted. Finally, we will assess the difference when using the minimally invasive strategy for each health effect (∆effect) compared to the conventional strategy (based on FDI) as the reference strategy. The same will be calculated for related costs (∆cost). The discount rate of 5% will be applied for costs and effects. We will perform deterministic and probabilistic sensitivity analyses to handle uncertainties. The net benefit will be calculated, and acceptability curves plotted using different willingness-to-pay thresholds. Using Markov models, a longer-term economic evaluation will be carried out with trial results extrapolated over a primary tooth lifetime horizon. Discussion The main trial is ongoing, and data collection is still not finished. Therefore, economic evaluation has not commenced. We hypothesize that conventional strategy will be associated with more need for replacements of restorations in primary molars. These replacements may lead to more reinterventions, leading to higher costs after 2 years. The health effects will be a crucial aspect to take into account when deciding whether the minimally invasive strategy will be more efficient in allocating resources than the conventional strategy when considering the management of restorations in primary teeth. Finally, patients/parents preferences and consequent utility values may also influence this final conclusion about the economic aspects of implementing the minimally invasive approach for managing restorations in clinical practice. Therefore, these trial-based economic evaluations may bring actual evidence of the economic impact of such interventions. Trial registration NCT03520309. Registered May 9, 2018. Economic evaluations (the focus of this plan) are not initiated at the moment