Low PRKAB2 Expression Is Associated with Poor Outcomes in Pediatric Adrenocortical Tumors, and Treatment with Rottlerin Increases the PRKAB2 Level and Inhibits Tumorigenic Aspects in the NCI-H295R Adrenocortical Cancer Cell Line.

Pediatric adrenocortical tumors (ACTs) are rare, highly heterogeneous neoplasms with limited therapeutic options, making the investigation of new targets with potential therapeutic or prognostic purposes urgent. The PRKAB2 gene produces one of the subunits of the AMP-activated protein kinase (AMPK) complex and has been associated with cancer. However, little is known about the role AMPK plays in ACTs. We have evaluated how PRKAB2 is associated with clinical and biological characteristics in 63 pediatric patients with ACTs and conducted in vitro studies on the human NCI-H295R ACC cell line. An analysis of our cohort and the public ACC pediatric dataset GSE76019 showed that lower PRKAB2 expression was associated with relapse, death, metastasis, and lower event-free and overall survival rates. Multivariate analysis showed that PRKAB2 expression was an independent prognostic factor when associated with age, tumor weight and volume, and metastasis. In vitro tests on NCI-H295R cells demonstrated that Rottlerin, a drug that can activate AMPK, modulated several pathways in NCI-H295R cells, including AMPK/mTOR, Wnt/ß-catenin, SKP2, HH, MAPK, NFKB, and TNF. Treatment with Rottlerin decreased cell proliferation and migration, clonogenic capacity, and steroid production. Together, these results suggest that PRKAB2 is a potential prognostic marker in pediatric ACTs, and that Rottlerin is promising for investigating drugs that can act against ACTs.

Musashi-1 regulates cell cycle and confers resistance to cisplatin treatment in Group 3/4 medulloblastomas cells.

Groups (Grp) 3 and 4 are aggressive molecular subgroups of medulloblastoma (MB), with high rates of leptomeningeal dissemination. To date, there is still a paucity of biomarkers for these subtypes of MBs. In this study, we investigated the clinical significance and biological functions of Musashi-1 (MSI1) in Grp3 and Grp4-MBs. First, we assessed the expression profile of MSI1 in 59 primary MB samples (15-WNT, 18-SHH, 9-Grp3, and 17-Grp4 subgroups) by qRT-PCR. MSI1 mRNA expression levels were also validated in an additional public dataset of MBs (GSE85217). The ROC curve was used to validate the diagnostic standards of MSI1 expression. Next, the potential correlated cell-cycle genes were measured by RNA-Seq. Cell cycle, cell viability, and apoptosis were evaluated in a Grp3/Grp4 MB cell line after knockdown of MSI1 and cisplatin treatment. We identified an overexpression of MSI1 with a high accuracy to discriminate Grp3/Grp4-MBs from non-Grp3/Grp4-MBs. We identified that MSI1 knockdown not only triggered transcriptional changes in the cell-cycle pathway, but also affected G2/M phase in vitro, supporting the role of knockdown of MSI1 in cell-cycle arrest. Finally, MSI1 knockdown decreased cell viability and sensitized D283-Med cells to cisplatin treatment by enhancing cell apoptosis. Based on these findings, we suggest that MSI1 modulates cell-cycle progression and may play a role as biomarker for Grp3/Grp4-MBs. In addition, MSI1 knockdown combined with cisplatin may offer a potential strategy to be further explored in Grp3/Grp4-MBs.

Clinical Prognostic Implications of Wnt Hub Genes Expression in Medulloblastoma.

Medulloblastoma is the most common type of pediatric malignant primary brain tumor, and about one-third of patients die due to disease recurrence and most survivors suffer from long-term side effects. MB is clinically, genetically, and epigenetically heterogeneous and subdivided into at least four molecular subgroups: WNT, SHH, Group 3, and Group 4. We evaluated common differentially expressed genes between a Brazilian RNA-seq GSE181293 dataset and microarray GSE85217 dataset cohort of pediatric MB samples using bioinformatics methodology in order to identify hub genes of the molecular subgroups based on PPI network construction, survival and functional analysis. The main finding was the identification of five hub genes from the WNT subgroup that are tumor suppressors, and whose lower expression is related to a worse prognosis for MB patients. Furthermore, the common genes correlated with the five tumor suppressors participate in important pathways and processes for tumor initiation and progression, as well as development and differentiation, and some of them control cell stemness and pluripotency. These genes have not yet been studied within the context of MB, representing new important elements for investigation in the search for therapeutic targets, prognostic markers or for understanding of MB biology.

Carga económica de la degeneración macular neovascular y el edema macular diabético en Colombia / Economic burden of neovascular macular degeneration and diabetic macular edema in Colombia

Antecedentes: La pérdida de visión tiene consecuencias tanto en la salud como en la estabilidad económica, ya que promueve retrasos en el desarrollo emocional, social, además de reducciones en la productividad laboral. Objetivo: Estimar la carga económica de la degeneración macular asociada a la edad neovascular (DMAEn) y el edema macular diabético (EMD) en Colombia para el año 2022. Método: Para una perspectiva social se incluyeron costos directos utilizando la aproximación de Bottom-up y costos indirectos relacionados con la pérdida de productividad. Resultados: El costo directo de un paciente con DMAEn fue 5.974 USD$ desde una base teórica. A nivel nacional, la DMAEn costaría 179,9 millones USD$. Los costos indirectos de DMAEn se estimaron en 13,9 millones USD$. Los costos directos teóricos en EMD fueron 741,6 millones USD$. El costo nacional sería de 132,04 millones USD$. Para los costos indirectos de EMD, se estimó un costo de 93,3 millones USD$. Conclusiones: La DMAEn y el EMD tienen un alto impacto para el sistema de salud y la sociedad.

Background: The vision loss has consequences for both health and economic stability, since it promotes delays in emotional and social development, as well as reductions in labor productivity. Objective: To estimate the economic burden of age-related macular degeneration (AMD) and diabetic macular edema (DME) in Colombia for 2022. Method: For a social perspective, direct costs were included using the bottom-up approach, and indirect costs related to lost productivity. Results: The direct costs of treating a patient with AMD were USD $5,974 from a theoretical background. At national level, the AMD would cost USD $179.9 million. The AMD indirect cost in Colombia was estimated in USD $13.9 million. Patients theoretical direct cost of DME was USD $741.6 million. The cost at national level is USD $132.04 million. Regarding the indirect costs result for DME, a cost of USD $93.31 million was estimated. Conclusions: The AMD and the DME have a considerable impact on the health system and society.

MicroRNA-149-3p expression correlates with outcomes of adrenocortical tumor patients and affects proliferation and cell cycle progression of H295A adrenocortical cancer cell line.

Pediatric adrenocortical tumor (ACT) is a rare and aggressive neoplasm, with incidence in southern and southeastern Brazil 10-15 times higher than worldwide. Although microRNAs (miRNAs) have been reported to act as tumor suppressors or oncogenes in several cancers, the role of miR-149-3p in ACT remains unknown. In this study, we evaluated the expression of miR-149-3p in 67 pediatric ACT samples and 19 non-neoplastic adrenal tissues. The overexpression of miR-149-3p was induced in H295A cell line, and cell viability, proliferation, colony formation, and cell cycle were assessed by in miR-149-3p mimic or mimic control. In silico analysis were used to predict miR-149-3p putative target genes. CDKN1A expression at the mRNA and protein levels was evaluated by qRT-PCR and western blot, respectively. Higher miR-149-3p expression was associated with unfavorable ACT outcomes. Compared to the mimic control, miR-149-3p overexpression increased cell viability and colony formation, and affected cell cycle progression. Also, we identified CDKN1A as a potential miR-149-3p target gene, with decreased expression at both the gene and protein levels in miR-149-3p mimic cells. Collectively, these findings suggest that miR-149-3p promotes H295A cell viability by downregulating CDKN1A and provide evidence that miR-149-3p may be useful as a novel therapeutic target for pediatric ACT.

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis.

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.

Facial Seborrheic Dermatitis in HIV-Seropositive Patients: Evaluation of the Efficacy and Safety of a Non-Steroidal Cream Containing Piroctone Olamine, Biosaccharide Gum-2 and Stearyl Glycyrrhetinate - A Case Series.

Facial seborrheic dermatitis is common in HIV-positive patients, and the presence of facial lesions can affect quality of life. The management and control of lesions can be frustrating for both physicians and patients. In this pilot clinical study, we clinically evaluated the effectiveness of a topical non-steroidal cream in treating mild to moderate facial seborrheic dermatitis in 20 HIV-positive patients. The patients applied a twice-a-day topical cream containing zinc PCA, piroctone olamine, hydroxyphenyl propamidobenzoic acid, biosaccharide gum-2, and stearyl glycyrrhetinate for 12 weeks with no topical or oral antifungal or corticosteroid treatment. Signs and symptoms and tolerance were assessed before, during, and at the end of treatment. All of the patients showed clinical improvement after 4 and 12 weeks of treatment. None of the patients had no response to treatment, and no adverse effects were reported. No rescue therapy with corticosteroids was needed. The patients reported a very noticeable improvement in their skin which contributed to high compliance with the protocol requirement.

Identification of ITPR1 as a Hub Gene of Group 3 Medulloblastoma and Coregulated Genes with Potential Prognostic Values.

The Group 3 Medulloblastoma (Grp3-MB) is an aggressive molecular subtype with a high incidence of metastasis and deaths. In this study, were used an RNA sequencing data (RNA-Seq) from a Brazilian cohort of MBs to identify hub genes associated with the metastatic risk. Data validation were performed by using multiple large datasets from MBs (GSE85217, GSE37418, and EGAS00001001953). DESeq2 package in R software was used to identify the differentially expressed genes (DEGs) in our RNA-Seq data. The DEGs data were accessed to construct the modules/graphs of co-expression and to identify hub genes through Cytoscape platform. The coregulated genes were enriched by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the protein-protein interaction (PPI) network was visualized by Cytoscape. The Kaplan-Meier plotter and ROC curves were used to validate the diagnostic and prognostic values of specific biomarkers identified through this model. We identified that inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) as a downregulated hub gene, with a high diagnostic accuracy to Grp3-MBs and associated with tumor metastasis. In addition, we identified genes significantly correlated with ITPR1 that were associated with metastasis in Grp3-MB (ATP1A2, MTTL7A, and RGL1) and worst overall survival in MBs (ANTXR1 and RGL1). Our findings suggest that the ITPR1 hub gene is potentially involved in the metastatic process for Grp3-MB. Our data also provide evidence of targets that may serve as prognostic predictors and/or regulators for the metastatic process that maybe explored for further research of individualized therapy to Grp3-MBs.

MicroRNA expression profile predicts prognosis of pediatric adrenocortical tumors.

Pediatric adrenocortical tumors (ACT) are rare aggressive neoplasms with heterogeneous prognosis. Despite extensive efforts, identifying reliable prognostic factors for pediatric patients with ACT remains a challenge. MicroRNA (miRNA) signatures have been associated with cancer diagnosis, treatment response, and prognosis of several types of cancer. However, the role of miRNAs has been poorly explored in pediatric ACT. In this study, we performed miRNA microarray profiling on a cohort of 37 pediatric ACT and nine nonneoplastic adrenal (NNA) samples and evaluated the prognostic significance of abnormally expressed miRNAs using Kaplan-Meier plots, log-rank test, and Cox regression analysis. We identified a total of 98 abnormally expressed miRNAs; their expression profile discriminated ACT from NNAs. Among the 98 deregulated miRNAs, 17 presented significant associations with patients' survival. In addition, higher expression levels of hsa-miR-630, -139-3p, -125a-3p, -574-5p, -596, -564, -1321, and -423-5p and lower expression levels of hsa-miR-377-3p, -126-3p, -410, -136-3p, -29b-3p, -29a-3p, -337-5p, -143-3p, and 140-5p were significantly associated with poor prognosis, tumor relapse, and/or death. Importantly, the expression profile of these 17 miRNAs stratified patients into two groups of ACTs with different clinical outcomes. Although some individual miRNAs exhibit potential prognostic values in ACTs, only the 17 miRNA-based expression clustering was considered an independent prognostic factor for 5-year event-free survival (EFS) compared to other clinicopathological features. In conclusion, our study reports for the first time associations between miRNA profiles and childhood ACT prognosis, providing evidence that miRNAs could be useful biomarkers to discriminate patients with favorable and unfavorable clinical outcomes.

MSI2 expression in adrenocortical carcinoma: Association with unfavorable prognosis and correlation with steroid and immune-related pathways.

Adrenocortical carcinoma (ACC) is a rare, but highly aggressive cancer of the adrenal cortex with a generally poor prognosis. Despite being rare, completely resected ACCs present a high risk of recurrence. Musashi-2 (MSI2) has recently been recognized as a potential prognostic biomarker and therapeutic target in many cancers. However, no studies have evaluated the clinical significance of MSI2 expression in ACC. Here, we addressed MSI2 expression and its association with ACC prognosis and clinicopathological parameters. MSI2 expression was analyzed in TCGA, GSE12368, GSE33371, and GSE49278 ACC datasets; and its correlation with other genes and immune cell infiltration were investigated by using the R2: Genomics Analysis and Visualization Platform and TIMER databases, respectively. Enrichment analysis was performed with the DAVID Functional Annotation Tool. Kaplan-Meier curves, log-rank tests, and Cox regression analyses were used to explore the prognostic role of MSI2 in ACC. Our findings demonstrated the potential value of MSI2 overexpression as an independent predictor of poor prognosis in patients with completely resected ACC (hazard ratio 6.715, 95% confidence interval 1.266 - 35.620, p =.025). In addition, MSI2 overexpression was associated with characteristics of unfavorable prognosis, such as cortisol excess (p = .002), recurrence (p =.003), and death (p =.015); positively correlated with genes related to steroid biosynthesis (p < .05); and negatively correlated with immune-related pathways (p < .05). Our findings demonstrate that MSI2 has value as a prognostic marker for completely resected ACC and reinforce the investigation of its role as a possible therapeutic target for patients with ACC.

In vitro and in vivo activity of a hypotoxic copper(I) complex against dermotropic Leishmania species / Atividade in vitro e in vivo de um complexo de cobre(I) hipotóxico contra espécies dermotrópicas de Leishmania

Cutaneous leishmaniasis is a disease caused by protozoa of the genus Leishmania and, currently, the treatment of first choice is meglumine antimoniate. However, due to its limited effectiveness and high toxicity, it is necessary to seek new active principles for leishmaniasis treatment. Metal complexes are gaining importance due to their effectiveness and low toxicity. In this context, the present study aimed to evaluate the in vitro and in vivo antileishmanial activity of the hypotoxic copper(I) complex [HB(pz)3]Cu(PCN). Four dermotropic species of Leishmania were tested with the metal complex and its effectiveness was determined through parasitic viability and infectivity rate, and cytotoxicity was determined using a redox dye (resazurin). For the in vivo tests, hamsters were infected and the lesions treated with a formulated ointment containing the complex, the effectiveness of which was assessed by measuring the diameter of the inoculum/snout location and determining the parasitic load. The results demonstrated moderate toxicity in murine macrophages and human monocytes and better efficacy in Leishmania (V.) braziliensis when compared to the other species tested, with a 50% reduction in the viability of promastigote and amastigote forms (in vitro). General data from daily topical treatment for up to 30 days showed low efficacy for reducing lesions, and no clinical and parasitological cure was observed in the experimental animals. Thus, the [HB(pz)3]Cu(PCN) complex proved to be promising in in vitro studies against L. (V.) braziliensis, and should be further tested in new formulations and new experimental treatment schemes.

A leishmaniose cutânea é uma doença causada por protozoários do gênero Leishmania e, atualmente, o tratamento de primeira escolha é o antimoniato de meglumina. Porém, devido à sua eficácia limitada e alta toxicidade, é necessário buscar novos princípios ativos para o tratamento da leishmaniose. Os complexos metálicos vêm ganhando importância devido à sua eficácia e baixa toxicidade. Nesse contexto, o presente estudo teve como objetivo avaliar a atividade leishmanicida in vitro e in vivo do complexo hipotóxico de cobre(I) [HB(pz)3]Cu(PCN). Quatro espécies dermotrópicas de Leishmania foram testadas com o complexo metálico e sua eficácia foi determinada através da viabilidade parasitária e taxa de infectividade, e a citotoxicidade foi determinada com um corante redox (resazurina). Para os testes in vivo, hamsters foram infectados e as lesões foram tratadas com uma pomada formulada contendo o complexo. A eficácia foi avaliada medindo o diâmetro do inóculo/focinho e determinando a carga parasitária. Os resultados demonstraram toxicidade moderada em macrófagos murinos e monócitos humanos e melhor eficácia em Leishmania (V.) braziliensis quando comparada às demais espécies testadas, com redução de 50% na viabilidade das formas promastigotas e amastigotas (in vitro). Os dados gerais do tratamento tópico diário por até 30 dias mostraram baixa eficácia na redução das lesões, e nenhuma cura clínica e parasitológica foi observada nos animais experimentais. Portanto, o complexo [HB(pz)3]Cu(PCN) mostrou-se promissor em estudos in vitro contra L. (V.) braziliensis, devendo ser empregado em novas formulações e novos esquemas de tratamento experimental.

Residual lesions in patients undergoing microsurgical clipping of cerebral aneurysms in a reference university hospital.

OBJECTIVES: This study aimed to analyze the incidence and epidemiological, angiographic, and surgical aspects associated with incomplete clipping of brain aneurysms in a cohort of patients undergoing microsurgical treatment. METHODS: The medical record data of patients who underwent microsurgery for cerebral aneurysm treatment and postoperative digital subtraction angiography, treated at the same teaching hospital between 2014 and 2019, were retrospectively analyzed. The studied variables involved epidemiological and clinical data, as well as neurological status and findings on neuroimaging. The time elapsed between hemorrhage and microsurgical treatment, data on the neurosurgical procedure employed for aneurysm occlusion, and factors associated with the treated aneurysm, specifically location and size, were also evaluated. RESULTS: One hundred and seventeen patients were submitted to 139 neurosurgical procedures, in which 167 aneurysms were clipped. The overall rate of residual injury was 23%. Smoking (odds ratio [OR]: 3.38, 95% confidence interval [CI95%]: 1.372-8.300, p=0.008), lesion size >10 mm (OR: 5.136, CI95%: 2.240-11.779, p<0.001) and surgery duration >6 h (OR: 8.667, CI95%: 2.713-27.681, p<0.001) were found to significantly impact incomplete aneurysm occlusion in the univariate analyses. CONCLUSION: Incomplete microsurgical aneurysm occlusion is associated with aneurysm size, complexity, and current smoking status. Currently, there is no consensus on postoperative assessment of clipped aneurysms, hindering the correct assessment of treatment outcomes.

COVID-19 and the eye: how much do we really know? A best evidence review.

To identify and classify available information regarding COVID-19 and eye care according to the level of evidence, within four main topics of interest: evidence of the virus in tears and the ocular surface, infection via the conjunctival route, ocular manifestations, and best practice recommendations. A structured review was conducted in PubMed, ScienceDirect, LILACS, SciELO, the Cochrane Library and Google Scholar on COVID-19 and ophthalmology. The Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence worksheet was used for quality assessments. 1018 items were identified in the search; 26 records were included in the qualitative synthesis, which encompassed 6 literature reviews, 10 case series or cross-sectional studies, 4 case reports, and 6 intervention descriptions. Seventeen out of 26 records (65%) were categorized as level 5 within the Oxford CBME methodology grading system, the rest were level 4. The evidence generated on COVID-19 and ophthalmology to date is limited, although this is understandable given the circumstances. Both the possible presence of viral particles in tears and conjunctiva, and the potential for conjunctival transmission remain controversial. Ocular manifestations are not frequent and could resemble viral infection of the ocular surface. Most recommendations are based on the strategies implemented by Asian countries during previous coronavirus outbreaks. There is a need for substantive studies evaluating these strategies in the setting of SARS-CoV-2. In the meantime, plans for applying these measures must be implemented with caution, taking into account the context of each individual country, and undergo regular evaluation.

COVID-19 and the eye: how much do we really know? A best evidence review / COVID-19 e o olho: quanto sabemos realmente? Uma revisão das melhores evidências

ABSTRACT To identify and classify available information regarding COVID-19 and eye care according to the level of evidence, within four main topics of interest: evidence of the virus in tears and the ocular surface, infection via the conjunctival route, ocular manifestations, and best practice recommendations. A structured review was conducted in PubMed, ScienceDirect, LILACS, SciELO, the Cochrane Library and Google Scholar on COVID-19 and ophthalmology. The Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence worksheet was used for quality assessments. 1018 items were identified in the search; 26 records were included in the qualitative synthesis, which encompassed 6 literature reviews, 10 case series or cross-sectional studies, 4 case reports, and 6 intervention descriptions. Seventeen out of 26 records (65%) were categorized as level 5 within the Oxford CBME methodology grading system, the rest were level 4. The evidence generated on COVID-19 and ophthalmology to date is limited, although this is understandable given the circumstances. Both the possible presence of viral particles in tears and conjunctiva, and the potential for conjunctival transmission remain controversial. Ocular manifestations are not frequent and could resemble viral infection of the ocular surface. Most recommendations are based on the strategies implemented by Asian countries during previous coronavirus outbreaks. There is a need for substantive studies evaluating these strategies in the setting of SARS-CoV-2. In the meantime, plans for applying these measures must be implemented with caution, taking into account the context of each individual country, and undergo regular evaluation.

RESUMO Identificar e classificar as informações disponíveis sobre o COVID-19 e o tratamento oftalmológico de acordo com o nível de evidência, dentro de quatro tópicos principais de interesse: evidência do vírus nas lágrimas e na superfície ocular, infecção pela via conjuntival, manifestações oculares e recomendações de melhores práticas. Foi realizada uma revisão estruturada no PubMed, ScienceDirect, LILACS, SciELO, Biblioteca Cochrane e Google Scholar no COVID-19 e oftalmologia. A planilha de Níveis de Evidência 2011 do Oxford Centre for Evidence Based Medicine 2011 foi usada para avaliações de qualidade. Mil e dezoito itens foram identificados na busca; Foram incluídos 26 registros na síntese qualitativa, que incluiu 6 revisões de literatura, 10 séries de casos ou estudos transversais, 4 relatos de casos e 6 descrições de intervenções. Dezessete dos 26 registros (65%) foram classificados como nível 5 no sistema de classificação da metodologia Oxford CBME, o restante foi no nível 4. As evidências geradas no COVID-19 e na oftalmologia até o momento são limitadas, embora isso seja compreensível dadas as circunstâncias. Tanto a possível presença de partículas virais em lágrimas e conjuntiva quanto o potencial de transmissão conjuntival permanecem controversos. As manifestações oculares não são frequentes e podem se assemelhar a infecção viral da superfície ocular. A maioria das recomendações baseia-se nas estratégias implementadas pelos países asiáticos durante surtos anteriores de coronavírus. Há necessidade de estudos aprofundados avaliando essas estratégias no cenário da SARS-CoV-2. Enquanto isso, os planos para a aplicação dessas medidas devem ser implementados com cautela, levando em consideração o contexto de cada país e submetidos a auditorias periódicas.

COVID-19 and the eye: how much do we really know? A best evidence review / COVID-19 e o olho: quanto sabemos realmente? Uma revisão das melhores evidências

To identify and classify available information regarding COVID-19 and eye care according to the level of evidence, within four main topics of interest: evidence of the virus in tears and the ocular surface, infection via the conjunctival route, ocular manifestations, and best practice recommendations. A structured review was conducted in PubMed, ScienceDirect, LILACS, SciELO, the Cochrane Library and Google Scholar on COVID-19 and ophthalmology. The Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence worksheet was used for quality assessments. 1018 items were identified in the search; 26 records were included in the qualitative synthesis, which encompassed 6 literature reviews, 10 case series or cross-sectional studies, 4 case reports, and 6 intervention descriptions. Seventeen out of 26 records (65%) were categorized as level 5 within the Oxford CBME methodology grading system, the rest were level 4. The evidence generated on COVID-19 and ophthalmology to date is limited, although this is understandable given the circumstances. Both the possible presence of viral particles in tears and conjunctiva, and the potential for conjunctival transmission remain controversial. Ocular manifestations are not frequent and could resemble viral infection of the ocular surface. Most recommendations are based on the strategies implemented by Asian countries during previous coronavirus outbreaks. There is a need for substantive studies evaluating these strategies in the setting of SARS-CoV-2. In the meantime, plans for applying these measures must be implemented with caution, taking into account the context of each individual country, and undergo regular evaluation.

Identificar e classificar as informações disponíveis sobre o COVID-19 e o tratamento oftalmológico de acordo com o nível de evidência, dentro de quatro tópicos principais de interesse: evidência do vírus nas lágrimas e na superfície ocular, infecção pela via conjuntival, manifestações oculares e recomendações de melhores práticas. Foi realizada uma revisão estruturada no PubMed, ScienceDirect, LILACS, SciELO, Biblioteca Cochrane e Google Scholar no COVID-19 e oftalmologia. A planilha de Níveis de Evidência 2011 do Oxford Centre for Evidence Based Medicine 2011 foi usada para avaliações de qualidade. Mil e dezoito itens foram identificados na busca; Foram incluídos 26 registros na síntese qualitativa, que incluiu 6 revisões de literatura, 10 séries de casos ou estudos transversais, 4 relatos de casos e 6 descrições de intervenções. Dezessete dos 26 registros (65%) foram classificados como nível 5 no sistema de classificação da metodologia Oxford CBME, o restante foi no nível 4. As evidências geradas no COVID-19 e na oftalmologia até o momento são limitadas, embora isso seja compreensível dadas as circunstâncias. Tanto a possível presença de partículas virais em lágrimas e conjuntiva quanto o potencial de transmissão conjuntival permanecem controversos. As manifestações oculares não são frequentes e podem se assemelhar a infecção viral da superfície ocular. A maioria das recomendações baseia-se nas estratégias implementadas pelos países asiáticos durante surtos anteriores de coronavírus. Há necessidade de estudos aprofundados avaliando essas estratégias no cenário da SARS-CoV-2. Enquanto isso, os planos para a aplicação dessas medidas devem ser implementados com cautela, levando em consideração o contexto de cada país e submetidos a auditorias periódicas.

The adverse effects of radiotherapy on the structure of dental hard tissues and longevity of dental restoration.

Purpose: The main goal of this study was to evaluate the impact of different ionizing radiation doses on the mineral (carbonate/phosphate ratio, crystallinity index [CI]) and organic (amide III/phosphate, amide I sub-band ratios) structures, as well as the microhardness, of enamel and dentin, along with their influence on the bonding strength stability of the etch-and-rinse (ER) and self-etch (SE) dental adhesive strategies.Materials and methods: Enamel and dentin human tissue specimens were irradiated (with 0, 20, 40, and 70 Gy radiation doses, respectively) and sectioned to perform an attenuated total reflection-Fourier transform IR spectroscopy assay (ATR-FTIR) and the Vickers microhardness (VHN) test to conduct a biochemical and biomechanical evaluation of the tissues. Regarding the adhesive properties, restored enamel and dentin specimens exposed to the same radiation doses were submitted to microshear bond strength (µSBS) tests for enamel in immediate time (IM) and to microtensile bond strength (µTBS) tests after for IM and 12-month (12 M) period of time, Mann-Whitney U tests were implemented, using the ATR-FTIR data for significant differences (α < 0.05), and three- and two-way analyses of variance, along with post-testing, were performed on the µTBS and µSBS data (MPa), respectively (Tukey post hoc test at α = 0.05).Results: The ATR-FTIR results showed a significant decrease (p < .05) in the amide III/phosphate ratio after 20 Gy for the enamel and after 40 Gy for the dentin. The CI was significantly reduced for both tissues after a dose of 70 Gy (p < .05). All radiation doses significantly decreased microhardness values, relative to the respective enamel and dentin controls (p < .05). In both tissues and adhesive strategies, the decrease in bond strength was influenced by ionizing radiation starting from 40 Gy. The ER strategy showed high percentages of enamel cohesive failure. In general, ER in both tissues showed greater and more stable bond strength than SE against increased radiation doses and long term.Conclusions: It is possible to conclude that structural alterations of enamel and dentin are generated by all radiation doses, decreasing the microhardness of dental hard tissues and influencing bond strength over time, starting at 40 Gy radiation dose. The etch-and-rinse strategy demonstrates better adhesive performance but generates cohesive fractures in the enamel.

Residual lesions in patients undergoing microsurgical clipping of cerebral aneurysms in a reference university hospital

OBJECTIVES: This study aimed to analyze the incidence and epidemiological, angiographic, and surgical aspects associated with incomplete clipping of brain aneurysms in a cohort of patients undergoing microsurgical treatment. METHODS: The medical record data of patients who underwent microsurgery for cerebral aneurysm treatment and postoperative digital subtraction angiography, treated at the same teaching hospital between 2014 and 2019, were retrospectively analyzed. The studied variables involved epidemiological and clinical data, as well as neurological status and findings on neuroimaging. The time elapsed between hemorrhage and microsurgical treatment, data on the neurosurgical procedure employed for aneurysm occlusion, and factors associated with the treated aneurysm, specifically location and size, were also evaluated. RESULTS: One hundred and seventeen patients were submitted to 139 neurosurgical procedures, in which 167 aneurysms were clipped. The overall rate of residual injury was 23%. Smoking (odds ratio [OR]: 3.38, 95% confidence interval [CI95%]: 1.372-8.300, p=0.008), lesion size >10 mm (OR: 5.136, CI95%: 2.240-11.779, p<0.001) and surgery duration >6 h (OR: 8.667, CI95%: 2.713-27.681, p<0.001) were found to significantly impact incomplete aneurysm occlusion in the univariate analyses. CONCLUSION: Incomplete microsurgical aneurysm occlusion is associated with aneurysm size, complexity, and current smoking status. Currently, there is no consensus on postoperative assessment of clipped aneurysms, hindering the correct assessment of treatment outcomes.

Comunidades desplazadas en Medellín: un Estado ausente, unas mujeres reconstruidas / Displaced communities in Medellin: an absent State, some women reconstructed

Resumen Los conflictos armados afectan especialmente a las mujeres, quienes son una de las poblaciones más vulnerables de la sociedad. El objetivo de este artículo es analizar la percepción de las mujeres en situación de desplazamiento ubicadas en tres asentamientos de la ciudad de Medellín sobre su situación de salud/enfermedad, y la relación con los roles de género, durante los años 2013-2014. Para desarrollar la investigación se empleó un enfoque cualitativo y la Teoría Fundamentada como método. En conclusión, el desplazamiento se configura como una importante experiencia en la construcción del significado de la salud/enfermedad de las mujeres y sus familias; este binomio se estructura a partir de factores como la experiencia individual, las costumbres, el contexto en el que están inmersos, y las respuestas que el Estado ofrece como soluciones.

Abstract Armed conflicts affect especially women, who are one of the most vulnerable groups of society. The aim of this paper is to analyze the perception of women in situations of displacement in three settlements located in the city of Medellin, regarding their health/disease situation, and its relationship to gender roles, for the years 2013-2014. To develop the research a qualitative approach was applied, using the Grounded Theory method. In conclusion, displacement is configured as an important experience in the construction of the meaning of health/disease of women and their families, this binomial is structured from factors like the individual experience, customs, the context in which they are immersed , and the responses that the State offers as solutions.