Repurposing ciclopirox as a pharmacological chaperone active against congenital erythropoietic porphyria.

138 p.La porfiria eritropoyética congénita es una enfermedad rara autosómica recesiva producida por una actividad deficiente en la uroporfirinógeno III sintasa, la cuarta enzima de la ruta biosintética del grupo hemo. La enfermedad afecta a diversos órganos, llegando a ser potencialmente peligroso para la vida, careciendo actualmente de tratamientos curativos. Bioquímicamente, las mutaciones hereditarias de mayor frecuencia reducen la estabilidad del enzima, alterando su homeostasis, que, en última instancia, reducen la producción de grupo hemo intracelular. Esto da como resultado la acumulación de subproductos de uroporfirina que se distribuyen y depositan por todos los tejidos, agravando la patología con síntomas tales como fotosensibilidad de la piel y lesiones cutáneas fototóxicas desfigurantes. En el presente trabajo, demostramos como el sintético antifúngico y microbiano fármaco comercial denominado ciclopirox, se asocia al enzima estabilizándolo. Ciclopirox asiste al enzima mediante unión alostética, distante del centro activo, sin afectar, por tanto, a su función catalítica. El fármaco es capaz de reestablecer la actividad in vitro, in cellula e in vivo, llegando incluso a aliviar la mayoría de los síntomas clínicos en un modelo de ratón bona fide de la enfermedad, actuando a concentraciones sub-tóxicas, estableciendo una nueva línea de intervención terapéutica contra la porfiria eritropoyética congénita. Aplicable a la mayoría de las mutaciones sin sentido perjudiciales que causan esta devastadora enfermedad.CICbioGUNE. Excelencia Severo Ocho

Repurposing ciclopirox as a pharmacological chaperone active against congenital erythropoietic porphyria.

138 p.La porfiria eritropoyética congénita es una enfermedad rara autosómica recesiva producida por una actividad deficiente en la uroporfirinógeno III sintasa, la cuarta enzima de la ruta biosintética del grupo hemo. La enfermedad afecta a diversos órganos, llegando a ser potencialmente peligroso para la vida, careciendo actualmente de tratamientos curativos. Bioquímicamente, las mutaciones hereditarias de mayor frecuencia reducen la estabilidad del enzima, alterando su homeostasis, que, en última instancia, reducen la producción de grupo hemo intracelular. Esto da como resultado la acumulación de subproductos de uroporfirina que se distribuyen y depositan por todos los tejidos, agravando la patología con síntomas tales como fotosensibilidad de la piel y lesiones cutáneas fototóxicas desfigurantes. En el presente trabajo, demostramos como el sintético antifúngico y microbiano fármaco comercial denominado ciclopirox, se asocia al enzima estabilizándolo. Ciclopirox asiste al enzima mediante unión alostética, distante del centro activo, sin afectar, por tanto, a su función catalítica. El fármaco es capaz de reestablecer la actividad in vitro, in cellula e in vivo, llegando incluso a aliviar la mayoría de los síntomas clínicos en un modelo de ratón bona fide de la enfermedad, actuando a concentraciones sub-tóxicas, estableciendo una nueva línea de intervención terapéutica contra la porfiria eritropoyética congénita. Aplicable a la mayoría de las mutaciones sin sentido perjudiciales que causan esta devastadora enfermedad.CICbioGUNE. Excelencia Severo Ocho

A variational modification of the Harmonic Balance method to obtain approximate Floquet exponents

Producción CientíficaWe propose a modification of a method based on Fourier analysis to obtainthe Floquet characteristic exponents for periodic homogeneous linear systems,which shows a high precision. This modification uses a variational principle tofind the correct Floquet exponents among the solutions of an algebraic equation.Once we have these Floquet exponents, we determine explicit approximatedsolutions. We test our results on systems for which exact solutions are knownto verify the accuracy of our method including one-dimensional periodicpotentials of interest in quantum physics. Using the equivalent linear system,we also study approximate solutions for homogeneous linear equations withperiodic coefficients.Ministerio de Ciencia e Innovación (proyect PID2020-113406GB-I0), with funding from the European Union NextGenerationEU and Consejería de Educación through QCAYLE (PRTRC17.I1)National University of Rosario (Argentina) grant ING19/i40

A modified Lyapunov method and its applications to ODE

Producción CientíficaHere, we propose a method to obtain local analytic approximate solutions of ordinary differential equations with variable coefficients, or even some nonlinear equations, inspired in the Lyapunov method, where instead of polynomial approximations, we use truncated Fourier series with variable coefficients as approximate solutions. In the case of equations admitting periodic solutions, an averaging over the coefficients gives global solutions. We show that, under some restrictive condition, the method is equivalent to the Picard-Lindelöf method. After some numerical experiments showing the efficiency of the method, we apply it to equations of interest in physics, in which we show that our method possesses an excellent precision even with low iterations.Ministerio de Ciencia e Innovación with funding from the European Union NextGenerationEU (PRTRC17.I1)Ministerio de Ciencia e Innovación project (PID2020-113406GB-I00

Os impactos da Reforma Tributária no ambiente social e corporativo / Impacts of Tax Reform on the social and corporate environment

O atual sistema tributário brasileiro vem, a muito tempo, sendo motivos de críticas devido a sua alta complexidade, com um grande número de impostos e regras, além da alta carga tributária praticada no país, o que afeta diretamente empresas, o cidadão e consequentemente o desenvolvimento econômico do país. Diante disso, nos últimos anos cresceu a necessidade de uma reforma tributária, sendo que atualmente existem três propostas de reforma tributária em trânsito, sendo a PEC 45/2019, PEC 110/2019 e PL 3.887/20. Sendo assim, o presente estudo teve como objetivo a analisar o impacto social e corporativo das propostas de reforma tributária que tramitam no Congresso Nacional. Para tanto, realizou-se uma análise bibliográfica, utilizando-se de autores que tratam sobre o assunto, além dos textos das próprias propostas avaliadas. Ao fim, conclui-se que as propostas, embora apresentem alguns pontos divergentes, tem como principal objetivo a simplificação do sistema tributário, com a extinção de alguns impostos e a criação de um Impostos sobre Valor Agregado, unificando os que foram extintos. Embora esse seja um grande avanço para a criação de um sistema ideal, em nenhuma das propostas observou-se uma preocupação com a redução da carga tributária ou tratou sobre a capacidade contribuitiva, pontos igualmente necessários para uma sociedade empresarial e civil mais igualitária e para o desenvolvimento econômico do paí

Posterior Lingual Abscess; Report of Two Cases

The lingual abscess is rare due to several protective mechanisms against infection in this location. Concretely, the abscess in the base of the tongue (posterior lingual abscess) is even more exceptional. Its prompt detection is crucial to avoid potentially fatal airway complications. To familiarize physicians with this condition, we report 2 cases of posterior lingual abscess. Both were referred to our emergency department due to minor oropharyngeal complaints. Finally, both were diagnosed and required surgical drainage. The clinical evolution was successful: both were discharged in less than 72 hours and follow-up one week later confirmed clinical recover

Combination of toothbrushing and chlorhexidine compared with exclusive use of chlorhexidine to reduce the risk of ventilator-associated pneumonia: A systematic review with meta-analysis

This study aimed to compare the effectiveness of 0.12% chlorhexidine alone and 0.12% chlorhexidine in combination with toothbrushing to prevent ventilator-associated pneumonia (VAP) in mechanically ventilated patients. The Embase, Latin American and Caribbean Health Science Literature, PubMed, Scientific Electronic Library Online, Scopus, LIVIVO, Web of Science, Cochrane Library, OpenThesis, and Open Access Thesis and Dissertations databases were used. Only randomized controlled trials without restrictions on the year or language of publication were included. Two reviewers assessed the risk of bias using the Joanna Briggs Institute Critical Appraisal Tool. A meta-analysis using a random-effects model estimated the combined relative risk (RR). The Grading of Recommendations, Assessment, Development and Evaluations approach was used to assess the certainty of the evidence. Initially, 2,337 studies were identified, of which 4 were considered in the systematic review and 3 in the meta-analysis (total sample: 796 patients). The studies were published between 2009 and 2017. All eligible studies had a low risk of bias. The meta-analysis revealed that the risk of VAP was 24% lower in patients receiving chlorhexidine combined with toothbrushing than in those receiving chlorhexidine alone (RR: 0.76; 95% confidence interval: 0.55-1.06), with moderate certainty of evidence and without statistical significance. In conclusion, considering the limitations of this study, a standard protocol for the prevention of VAP is not yet recommended. More studies with larger sample sizes are needed to draw strong conclusions. However, considering that toothbrushing is a simple intervention, it should be a common practice in mechanically ventilated patients, especially among patients with coronavirus disease

Efficacy of the laser at low intensity on primary burning oral syndrome:a systematic review

Primary burning mouth syndrome (BMS) is a chronic clinical condition of idiopathic mainly characterized by pain and a burning sensation in the oral cavity. The application of laser at low intensity therapy is a treatment option. This systematic review evaluated the efficacy of laser therapy in treating symptoms of burning mouth syndrome. The study was formulated according to the PRISMA and Cochrane guidelines. Seven databases were used as primary sources of research. Only randomized controlled clinical trials were included. The efficacy of the therapy was estimated comparing the values of the visual and numerical scales of pain before and after laser treatment, through qualitative analysis. The search resulted in 348 records and only eight filled the eligibility criteria and were included. All studies evaluated pain and / or a burning sensation considering a time interval of two to ten weeks. The total sample consisted of 314 patients submitted to treatment: 123 from the control group, who participated with laser off or with the tip blocked, and 191 from the intervention group, treated with low-level laser therapy. The female gender stood out and the average age of the participants was 60.89 years. The main symptoms reported were pain and a burning sensation in the oral mucosa and tongue. The parameters adopted by the authors for laser treatment were diverse and the variables were not fully described in the published studies. Visual analog and numerical scales were used to assess symptoms and only three studies showed statistical significance. It is suggested that laser therapy may be an effective alternative in the treatment of BMS. New randomized clinical trials should consider well-established protocols to better understand the efficacy of laser therapy without confounding the effects

Preemptive use of intravenous ibuprofen to reduce postoperative pain after lower third molar surgery: a systematic review of randomized controlled trials

This study aimed to systematically review the literature to assess the effect of preemptive intravenous ibuprofen on pain reduction after lower third molar surgery. Nine databases (PubMed, Scopus, LILACS, SciELO, Embase, Web of Science, Cochrane, Open Gray, and Open Thesis) were used as sources of research, including “grey literature.” The protocol was registered in PROSPERO. Only randomized clinical trials evaluating the effects of preemptive intravenous ibuprofen on pain during and immediately after the extraction of lower third molars were included, without restrictions of year and language. Two reviewers independently performed the study selection, data extraction, and assessment of the risk of bias. The “Joanna Briggs Institute for Randomized Controlled Trials” tool was used to assess the risk of bias. Each study was categorized according to the percentage of positive responses to the questions corresponding to the assessment instrument. The results were measured narratively/descriptively. The initial search resulted in 3,257 records, of which only three studies (n=150 participants) met the eligibility criteria and were included in the qualitative analysis. All studies were published in 2019. The risk of bias ranged from low to moderate. Two studies found significant pain reduction within 48 h after the procedure. In conclusion, the use of preemptive intravenous ibuprofen for extracting third molars reduces pain and analgesic consumption after the surgical procedure

Accuracy of computer-aided image analysis in the diagnosis of odontogenic cysts:a systematic review

This study aimed to search for scientific evidence concerning the accuracy of computer-assisted analysis for diagnosing odontogenic cysts. A systematic review was conducted according to the PRISMA statements and considering eleven databases, including the grey literature. Protocol was registered in PROSPERO (CRD 42020189349). The PECO strategy was used to define the eligibility criteria and only studies involving diagnostic accuracy were included. Their risk of bias was investigated using the Joanna Briggs Institute Critical Appraisal tool. Out of 437 identified citations, five papers, published between 2006 and 2019, fulfilled the criteria and were included in this systematic review. A total of 5,264 images from 508 lesions, classified as radicular cyst, odontogenic keratocyst, lateral periodontal cyst, glandular odontogenic cyst, or dentigerous cyst, were analyzed. All selected articles scored low risk of bias. In three studies, the best performances were achieved when the two subtypes of odontogenic keratocysts (solitary or syndromic) were pooled together, the case-wise analysis showing a success rate of 100% for odontogenic keratocysts and radicular cysts, in one of them. In two studies, the dentigerous cyst was associated with the majority of misclassifications, and its omission from the dataset improved significantly the classification rates. The overall evaluation showed all studies presented high accuracy rates of computer-aided systems in classifying odontogenic cysts in digital images of histological tissue sections. However, due to the heterogeneity of the studies, a meta-analysis evaluating the outcomes of interest was not performed and a pragmatic recommendation about their use is not possible