Resumo A tradição de La Llorona, a mulher que lamentase, é um arquétipo geral nas culturas latino-americanas. Embora as histórias de La Llorona variem por país e região, a narração mais comum está associada ao folclore mexicano, no qual uma mulher angustiada chora por seus filhos afogados; em algumas versões, a morte é o resultado de sua ira assassina por ser traída por seu amante; em outros, a morte é o resultado de um acidente. Tradicionalmente, essas histórias servem como contos de advertência, muitas vezes posicionando as Latinas como forças trágicas em suas comunidades (Morales, 2010). No entanto, especialistas chicanos reconceptualizaram La Llorona como um símbolo do poder feminista. Este estudo autoetnográfico reflete sobre a história de La Llorona como uma metáfora para a "resistência das mulheres Latinas" na sociedade (Anzaldúa, 1987, p. 33) ou como Morales (2010, p. 3) afirma, "o voz clamando contra a injustiça". Especialmente a través da aplicação da teoria feminista chicana / latina e da epistemologia crítica, as autoras exploram os trabalhos de Gloria Anzaldúa, Nela Martínez Espinosa, Dolores Huerta e Nisia Floresta, que como autoras e políticas feministas Latinas usaram suas vozes para combater injustiças sociais em suas comunidades, e os autores refletem sobre como essas heroínas influenciaram suas próprias identidades como "mulheres que lamentam- se", como educadoras Latinas feministas que trabalham para uma pedagogia em prol da justiça social.

Resumen La tradición de La Llorona, la mujer que se lamenta, es un arquetipo generalizado en las culturas latinoamericanas. Si bien las historias de la Llorona varían según el país y la región, la narración más común está asociada con el folklore mexicano, en el cual una mujer angustiada llora por sus hijos ahogados; en algunas versiones, la muerte es el resultado de su ira asesina al ser traicionada por su amante; en otros, la muerte es el resultado de un accidente. Estas historias han servido tradicionalmente como cuentos de advertencia, a menudo posicionando a las latinas como fuerzas trágicas dentro de sus comunidades (Morales, 2010). Sin embargo, los especialistas chicanos han reconceptualizado a La Llorona como símbolo de poder feminista. Este estudio autoetnográfico reflexiona en base a la historia de La Llorona como una metáfora de la "resistencia de la mujer latina” en la sociedad (Anzaldúa, 1987, p. 33), o como afirma Morales (2010, p. 3) "la voz que clama contra la injusticia ". En especial a través de la aplicación de la teoría feminista Chicana/Latina y la epistemología crítica, las autoras exploran los trabajos de Gloria Anzaldúa, Nela Martínez Espinosa, Dolores Huerta y Nisia Floresta, las cuales como autoras y políticas Latinas feministas han utilizado sus voces para luchar contra las injusticias sociales en sus comunidades. Además, las autoras reflexionan sobre cómo estas heroínas han influenciado sus propias identidades como "mujeres que se lamentan", como feministas Latinas educadoras que trabajan por una pedagogía en favor de la justicia social.

Abstract The lore of La Llorona, the woman who wails, is a pervasive archetype in Latin American cultures. While stories vary by country and region, the most common telling is associated with Mexican folklore, in which an anguished woman cries for her drowned children-in some retellings, their death results from her murderous rage at being betrayed by her lover; in others their deaths result from an accident. These stories have traditionally served as cautionary tales, often positioning Latinas as tragic forces within their communities (Morales, 2010); however, Chicana scholars have reconceptualized La Llorona to symbolize a feminist power. This autoethnographic study reflects on the lore of La Llorona as a metaphor for a Latina’s “resistance in society” (Anzaldúa, 1987, p.33) or as Morales (2010, p.3) states, “the voice who cries out against injustice”. Specifically, through the application of Chicana/Latina feminist and critical epistemologies, the authors explore the works of Gloria Anzaldúa, Nela Martinez Espinosa, Dolores Huerta, and Nisia Floresta- Latina feminist authors and politicians, who have used their voices to fight injustices within their communities. Furthermore, the authors reflect upon how these heroines have influenced their own identities as “women who wail”-as feminist Latina educators who work toward a pedagogy for social justice.

ABSTRACT Objective: To compare the histological properties and stretch of colorectal mucosal grafts (CMG) and buccal mucosal grafts (BMG) and to evaluate the impact of age, medical comorbidity and tobacco use on these metrics. Materials and Methods: Samples of BMGs from patients undergoing augmentation urethroplasty were sent for pathologic review. CMGs were collected from patients undergoing elective colectomy. CMGs were harvested fresh, at full thickness from normal rectum/sigmoid. Patients with inflammatory bowel disease, prior radiation, or chemotherapy were excluded. Results: Seventy two BMGs and 53 CMGs were reviewed. While BMGs and CMGs were both histologically composed of mucosal (epithelium + lamina propria) and submucosal layers, the mucosal layer in CMG had crypts. The outer epithelial layers differed significantly in mean thickness (BMG 573μm vs. CMG 430μm, p=0.0001). Mean lamina propria thickness and submucosal layer thickness also differed significantly (BMG 135μm vs. CMG 400μm, p<0.0001; BMG 1090μm vs. CMG 808μm, p = 0.007, respectively). Mean delta stretch, as to length and width, was greater for CMG (118% x 72%) compared to BMGs (22% x 8%), both p<0.001. Conclusion: CMGs and BMGs significantly differ histologically in layer composition, width and architecture, as well as graft stretch. Given its elastic properties, CMG may be useful in covering large surface areas, but its thin epithelium, thick lamina propria and additional muscularis mucosal layer could impact graft take and contracture.

RESUMO A Iniciativa Global para o Câncer Infantil tem como objetivo aumentar a taxa de cura de crianças com câncer no mundo todo, melhorando o acesso a cuidados e a qualidade da assistência médica. A Organização Pan-Americana da Saúde (OPAS), o St. Jude Children's Research Hospital (St. Jude) e colaboradores uniram esforços para melhorar o desfecho de crianças com câncer na América Latina e no Caribe (ALC) no âmbito do marco CureAll. Neste artigo, descrevemos o processo de desenvolvimento de recursos regionais com o objetivo de acelerar a implementação da Iniciativa na ALC. Em março de 2021, a OPAS formou grupos de trabalho regionais para desenvolver projetos centrais alinhados com os pilares e facilitadores do CureAll. A partir das reuniões de diálogo regionais, foram criados sete grupos de trabalho: detecção precoce, enfermagem, atenção psicossocial, nutrição, cuidados de suporte, abandono do tratamento e cuidados paliativos. A OPAS organizou reuniões virtuais regulares sob a orientação e o apoio dos programas regionais e transversais do St. Jude e de mentores internacionais. Entre abril e dezembro de 2021, 202 especialistas multidisciplinares participaram de 43 reuniões virtuais para promover o diálogo entre as partes interessadas a fim de melhorar os desfechos do câncer infantil. Foram produzidos 14 materiais técnicos: quatro panoramas regionais, quatro documentos técnicos, dois cursos virtuais, um conjunto de perfis epidemiológicos nacionais, uma série de conteúdo educacional para pais e cuidadores e duas campanhas de comunicação. O diálogo e o compromisso contínuos da OPAS, do St. Jude, dos comitês de trabalho da ALC e dos colaboradores internacionais são bases essenciais para acelerar com sucesso a implementação da Iniciativa Global para o Câncer Infantil. Isso é possível por meio do desenvolvimento de materiais de relevância regional e mundial. São necessárias mais pesquisas e avaliações para determinar o impacto dessas estratégias e recursos nos resultados do câncer infantil na ALC e em outras regiões.

RESUMEN La Iniciativa Mundial contra el Cáncer Infantil tiene como objetivo aumentar a nivel mundial la tasa de curación del cáncer infantil mediante la mejora del acceso a la atención de salud y de su calidad. La Organización Panamericana de la Salud (OPS), el St. Jude Children’s Research Hospital y los colaboradores han aunado esfuerzos para mejorar los resultados en la población infantil con cáncer en América Latina y el Caribe valiéndose del marco CureAll. En este artículo describimos el proceso de elaboración de recursos regionales destinados a acelerar la aplicación de la Iniciativa Mundial en América Latina y el Caribe. En marzo del 2021, la OPS formó grupos de trabajo regionales para elaborar proyectos básicos que estuvieran en consonancia con los pilares y los elementos facilitadores del CureAll. De los diálogos regionales surgieron siete grupos de trabajo: detección temprana, enfermería, aspectos psicosociales, nutrición, tratamientos de apoyo, abandono del tratamiento y cuidados paliativos. La OPS organizó con regularidad reuniones virtuales en las que se contó con la tutoría y el apoyo de programas regionales o transversales del St. Jude Children’s Research Hospital y de mentores internacionales. Entre abril y diciembre del 2021 hubo 43 reuniones virtuales a las que asistieron 202 expertos multidisciplinarios, con el objetivo de promover el diálogo entre las partes interesadas para mejorar los resultados en materia de cáncer infantil. Se elaboraron catorce productos técnicos: cuatro panoramas regionales, cuatro documentos técnicos, dos cursos virtuales, un conjunto de perfiles epidemiológicos de países, una serie con contenidos educativos para padres y cuidadores y dos campañas de comunicación. El diálogo y el compromiso constantes de la OPS, el St. Jude Children’s Research Hospital, los comités de trabajo de América Latina y el Caribe y los colaboradores internacionales son las bases fundamentales para conseguir que se acelere la aplicación de la Iniciativa Mundial. Esto se puede lograr mediante la elaboración de materiales que resulten pertinentes a nivel regional y mundial. Son necesarias más investigaciones y evaluaciones para determinar el impacto que tienen estas estrategias y recursos en los resultados que se obtienen en el cáncer infantil en América Latina y el Caribe y en otras subregiones.

ABSTRACT The Global Initiative for Childhood Cancer (GICC) aims to increase the cure rate for children with cancer globally by improving healthcare access and quality. The Pan American Health Organization (PAHO), St. Jude Children’s Research Hospital (St. Jude), and collaborators have joined efforts to improve outcomes of children with cancer in Latin America and the Caribbean (LAC) using the CureAll framework. In this article, we describe the process of developing regional resources aimed at accelerating the GICC implementation in LAC. In March 2021, PAHO formed regional working groups to develop core projects aligned with CureAll pillars and enablers. Seven working groups emerged from regional dialogues: early detection, nursing, psychosocial, nutrition, supportive care, treatment abandonment, and palliative care. PAHO arranged regular online meetings under the mentorship and support of St. Jude regional/transversal programs and international mentors. Between April and December 2021, 202 multidisciplinary experts attended 43 online meetings to promote the dialogue between stakeholders to improve childhood cancer outcomes. Fourteen technical outputs were produced: four regional snapshots, four technical documents, two virtual courses, one set of epidemiological country profiles, one educational content series for parents/caregivers, and two communication campaigns. The ongoing dialogue and commitment of PAHO, St. Jude, LAC working committees, and international collaborators are essential foundations to successfully accelerate GICC implementation. This is achievable through the development of materials of regional and global relevance. Further research and evaluation are needed to determine the impact of these strategies and resources on childhood cancer outcomes in LAC and other regions.

Abstract Objective: To analyze aspects of sexual life and fertility desire among 46, XY DSD people, including those who changed their gender. Methods: It is a cross-sectional study including 127 adults (> 16 years of age) with 46, XY DSD (83 females; 44 males) from a Single Brazilian Tertiary-Care Medical Center. Results: Sexual fantasies and masturbation were more frequent in 46, XY DSD males, whereas orgasm and sexual life satisfaction were similar in both genders. More 46, XY DSD men than women had a long-term romantic relationship. 46, XY DSD women with prenatal androgen exposure reported more fear of being romantically rejected. External genitalia appearance at birth did not impact the sexuality of 46, XY DSD women after surgical genital treatment had been completed. Overall, the sexual life was similar between 46, XY men assigned as males and those who changed to the male gender. Regarding sexual orientation, most self-reported as heterosexual (91% and 92% of women and men, respectively). The desire for fertility had a similar prevalence in both genders, but more women than men considered infertility a barrier to a long-term romantic relationship. Twelve individuals (7 males) had children; 10 out of 12 have adopted children. Conclusion: Fertility desire was shared among 46, XY DSD people, regardless of gender. Prenatal androgen exposure reduced the desire for motherhood in 46, XY women. 46, XY DSD people who changed from female to male gender presented similar sexual parameters as those assigned as males. Among females, virilized genitalia at birth did not affect sexuality once the surgical treatment is completed.

Abstract Impediment to local anesthetic solution in the epidural space results in unsatisfactory pain relief during labor epidural. Patients with a history of back trauma and spinal instrumentation have increased rates of epidural failure due to patchy spread of local anesthetic with obliterated epidural space. Dual Epidural Catheters (DEC) can be used in such clinical scenarios with complete labor analgesia and improved patient satisfaction. We present the successful management of a parturient with vertebral fracture at risk for epidural failure and neurologic injury due to bone fragments and inserted cranial and caudal to the fractured vertebra using ultrasound to avoid neurologic sequelae. DEC (DEC satisfaction sequelae

The mechanical and thermal behavior of ultra-high molecular weight polyethylene (UHMWPE)/metallic quasicrystal powder (MQP) composites are evaluated at filler volume fractions ( ∅ f) of 0.01, 0.02, 0.06 and 0.15. MQP is based on an aluminum alloy, synthesized and characterized to act as a filler for UHMWPE. The preparation of the composites was conducted by compression molding. Morphological analysis reveals larger and smaller MPQ particles, being well distributed, and mechanically anchored in the matrix. The melting temperature was maintained after adding filler, while the crystallinity values decreased. When adding MQP, an improvement in thermal stability is observed by increases in both the initial and maximum weight loss rate temperatures (Tmax). However, when the temperature is about 700°C all composites present oxidation due to the MQP presence. The Pukansky model shows that the 0.06 MQP composites have better interfacial adhesion. This is confirmed by the Nicolais-Narkis equation. This contributes to an increase in the modulus of elasticity of the 0.06 MQP composite in respect to the others. The elongation at break was reduced for the 0.15 MQP composite. However, the higher volume fraction of MQP increased the stiffness of the UHMWPE, reflecting its potential for use as a reinforcement.

Abstract 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.

ABSTRACT Primary adrenal insufficiency (PAI) is characterized by the inability of the adrenal cortex to produce sufficient amounts of glucocorticoids and/or mineralocorticoids. Addison's disease (AD) and congenital adrenal hyperplasia (CAH) are the most frequent disorders in adults and children, respectively. Despite the diagnostic advances and the availability of glucocorticoid and mineralocorticoid replacements, adrenal crisis (AC) is still a potentially lethal condition contributing to the increased mortality, not only during the first year of life, but also throughout life. Failure in increasing glucocorticoid doses during acute stress, when greater amounts of glucocorticoids are required, can lead to AC and an increase morbimortality rate of PAI. Considering a mortality rate of 0.5 per 100 patient years, up to 1,500 deaths from AC are expected in Brazil in the coming decade, which represents an alarming situation. The major clinical features are hypotension and volume depletion. Nonspecific symptoms such as fatigue, lack of energy, anorexia, nausea, vomiting, and abdominal pain are common. The main precipitating factors are gastrointestinal diseases, other infectious disease, stressful events (e.g., major pain, surgery, strenuous physical activity, heat, and pregnancy), and withdrawal of glucocorticoid therapy. Suspected AC requires immediate therapeutic action with intravenous (iv) hydrocortisone, fluid infusion, monitoring support, and antibiotics if necessary. AC is best prevented through patient education, precocious identification and by adjusting the glucocorticoid dosage in stressor situations. The emergency card, warning about acute glucocorticoid replacement, has high value in reducing the morbidity and mortality of AC.

OBJECTIVES: Single nucleotide variants (SNVs) are the most common type of genetic variation among humans. High-throughput sequencing methods have recently characterized millions of SNVs in several thousand individuals from various populations, most of which are benign polymorphisms. Identifying rare disease-causing SNVs remains challenging, and often requires functional in vitro studies. Prioritizing the most likely pathogenic SNVs is of utmost importance, and several computational methods have been developed for this purpose. However, these methods are based on different assumptions, and often produce discordant results. The aim of the present study was to evaluate the performance of 11 widely used pathogenicity prediction tools, which are freely available for identifying known pathogenic SNVs: Fathmn, Mutation Assessor, Protein Analysis Through Evolutionary Relationships (Phanter), Sorting Intolerant From Tolerant (SIFT), Mutation Taster, Polymorphism Phenotyping v2 (Polyphen-2), Align Grantham Variation Grantham Deviation (Align-GVGD), CAAD, Provean, SNPs&GO, and MutPred. METHODS: We analyzed 40 functionally proven pathogenic SNVs in four different genes associated with differences in sex development (DSD): 17β-hydroxysteroid dehydrogenase 3 (HSD17B3), steroidogenic factor 1 (NR5A1), androgen receptor (AR), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). To evaluate the false discovery rate of each tool, we analyzed 36 frequent (MAF>0.01) benign SNVs found in the same four DSD genes. The quality of the predictions was analyzed using six parameters: accuracy, precision, negative predictive value (NPV), sensitivity, specificity, and Matthews correlation coefficient (MCC). Overall performance was assessed using a receiver operating characteristic (ROC) curve. RESULTS: Our study found that none of the tools were 100% precise in identifying pathogenic SNVs. The highest specificity, precision, and accuracy were observed for Mutation Assessor, MutPred, SNP, and GO. They also presented the best statistical results based on the ROC curve statistical analysis. Of the 11 tools evaluated, 6 (Mutation Assessor, Phanter, SIFT, Mutation Taster, Polyphen-2, and CAAD) exhibited sensitivity >0.90, but they exhibited lower specificity (0.42-0.67). Performance, based on MCC, ranged from poor (Fathmn=0.04) to reasonably good (MutPred=0.66). CONCLUSION: Computational algorithms are important tools for SNV analysis, but their correlation with functional studies not consistent. In the present analysis, the best performing tools (based on accuracy, precision, and specificity) were Mutation Assessor, MutPred, and SNPs&GO, which presented the best concordance with functional studies.

RESUMO Objetivo Avaliar e classificar escolares disléxicos visuais, considerando que, subtipos de dislexia do desenvolvimento não são diferenciados na maioria dos diagnósticos e que os mesmos incidem em uma abordagem generalizada. Método Estudo transversal, observacional, analítico composto de 80 escolares, divididos em dois grupos, GA (disléxicos) e GB (sem queixa de dificuldade de aprendizagem) aplicando o PROLEC (prova de avaliação dos processos de leitura), o TVPS–3 (Teste Visual de Habilidades Perceptuais) e TPMBO (Teste de Proficiência Motora de Bruininks-Oseretsky) – subtestes 7 e 8. Resultados Comparando os grupos, os escolares do GA apresentaram desempenho inferior em todas as provas do PROLEC e no teste do TVPS−3. A execução nos testes de coordenação visuomotora e destreza manual do TPMBO foram inferiores. Em uma segunda etapa, triando os disléxicos visuais foram encontrados 12 (30%) escolares, que apresentaram melhor desempenho na leitura de palavras frequentes, quando comparados ao desempenho na leitura de palavras não frequentes e pseudopalavras. Nas habilidades perceptuais visuais (TVPS-3), obtiveram valores abaixo de 50%, exceto na subescala constância de forma. As ocorrências de trocas na leitura em voz alta, foram em confusão de letras, silabas ou palavras com pouca diferença na forma de escrever, mas diferentes na direção, os mesmos escolares não apresentaram trocas ou confusões entre letras, que possuem mesmo ponto e modo articulatório, e cujos sons são acusticamente próximos. Conclusão Assim caracterizar o subtipo da dislexia é fundamental, porque a aplicação das técnicas terapêuticas, dependerá do correto enfoque das alterações observadas. Portanto, é necessário um diagnóstico exato e multidisciplinar.

ABSTRACT Purpose to evaluate and classify visual dyslexic students, considering that developmental dyslexia subtypes are not differentiated in most diagnoses and that they affect a generalized approach. Methods Cross-sectional, observational, analytical study composed of 80 students, divided into two groups, GA (dyslexics) and GB (without complaints of learning difficulties) using PROLEC (proof of assessment of reading processes), TVPS – 3 (Visual Test of Perceptual Skills) and TPMBO (Bruininks-Oseretsky Motor Proficiency Test) - subtests 7 and 8. Results Comparing the groups, the students of GA presented inferior performance in all the PROLEC tests and in the TVPS3 tests. The TPMBO tests of visuomotor coordination and manual dexterity tests were inferior. In a second stage, screening the visual dyslexics, 12 (30%) schoolchildren were found, who presented better performance in reading frequent words, when compared to the performance in reading infrequent words and pseudowords. In the visual perceptual skills (TVPS-3), they obtained values below 50%, except for the subscale constancy of form. The occurrences of exchanges in reading aloud were in confusion of letters, syllables or words with little difference in the way of writing, but different in the direction, the same students did not present exchanges or confusions between letters, which have the same point and manner of articulation, and whose sounds are acoustically close. Conclusion Thus, characterizing the dyslexia subtype is fundamental, because the application of therapeutic techniques will depend on the correct focus of the observed changes. Therefore, an accurate and multidisciplinary diagnosis is required.

RESUMEN Bixa orellana L. es ampliamente utilizado como un tinte y tiene otras propiedades que han sido poco estudiadas, especialmente en relación con las hojas. Este artículo evalúa cómo el secado B. orellana L. influye en las propiedades de los aceites esenciales (EOs) extraídos de sus hojas. El material vegetal recogido se sometió al horno de secado por aire convectivo a temperaturas de 35, 45 y 55 °C. Los perfiles químicos fueron determinados por GC-MS. Se aplicaron modelos matemáticos para representar el proceso de secado y el análisis estadístico realizado utilizando el software Statistica 10. Las EO se obtuvieron a través de la técnica de hidrodestilación con verificación de propiedades fisicoquímicas y actividad antimicrobiana. Para el ensayo de toxicidad se aplicó el bioensayo a Artemia salina. A través de los resultados obtenidos fue posible determinar el modelo matemático que se ajustaba mejor. Se observaron diferencias significativas en las propiedades de los EO. La temperatura de 45 °C permitió obtener el mejor rendimiento de EO, porque la actividad antimicrobiana fue más eficiente. Este estudio afirma a través de las actividades analizadas que la temperatura de secado influye en las propiedades fisicoquímicas y biológicas de las EO. Estudios como este evalúan el mejor modelo matemático para predecir el secado, así como las temperaturas específicas que influyen en las propiedades del producto obtenido.

SUMMARY Bixa orellana L. is widely used as a dye, and other properties are still little studied, especially in relation to leaves. This article evaluates how drying B. orellana L. influences the properties of essential oils (EOs) extracted from their leaves. The collected plant material was submitted to convective air-drying oven at temperatures of 35, 45 and 55 °C. Chemical profiles were determined by Gas Chromatography-Mass Spectrometry (GC-MS). Mathematical models were applied to represent the drying process and statistical analysis performed using Statistica 10 software. The EO's were obtained through the hydrodistillation technique with verification of physicochemical properties and antimicrobial activity by the Disc Diffusion Method. For the toxicity test, the bioassay was applied to Artemia salina. Through the results obtained it was possible to determine that the mathematical model of Verma was the one that best fitted the experimental data. Significant differences in the properties of EO's were observed. The temperature of 45 °C allowed obtaining the best EO yield, still presenting the most efficient antimicrobial activity. This study states through the activities analyzed that the drying temperature influences the physicochemical and biological properties of the EO's, thus requiring studies such as this one that evaluate the best mathematical model to predict drying as well as the specific temperatures that influence the properties of the product obtained.

Resumo Fundamento: A segurança e a eficácia da varfarina dependem da qualidade do controle da anticoagulação. Estudos observacionais associam controle deficiente com aumento de morbidade, mortalidade e custos com saúde. Objetivos: Desenvolver um perfil de pacientes com fibrilação atrial não valvar (FANV) tratados com varfarina em ambiente ambulatorial e hospitalar privado brasileiro, avaliar a qualidade do controle da anticoagulação e sua associação com resultados clínicos e econômicos. Métodos: Este estudo retrospectivo, por meio de um conjunto de dados de seguros privados de saúde no Brasil, identificou pacientes com FANV tratados com varfarina entre 01 de maio de 2014 a 30 de abril de 2016, descreveu seu manejo da anticoagulação e quantificou os custos relacionados à doença. Foram recuperados dados demográficos, histórico clínico, medicação concomitante e tempo na faixa terapêutica (TTR) dos valores da razão normalizada internacional (RNI). Os pacientes foram agrupados em quartis de TTR, com um bom controle sendo definido como TTR ≥65% (método de Rosendaal). Sangramentos maiores e custos médicos diretos por todas as causas foram calculados e comparados entre subgrupos de controle bons e ruins. Valores de p < 0,05 foram considerados estatisticamente significantes. Resultados: A análise incluiu 1220 pacientes (mediana de seguimento: 1,5 anos; IIQ: 0,5-2,0). Em média, cada paciente recebeu 0,95 medidas mensais de RNI (RNI média: 2,60 ± 0,88, com 26,1% dos valores < 2 e 24,8% > 3), (mediana de TTR: 58%; IIQ: 47-68%), (TTR médio: 56,6% ± 18,9%). Apenas 31% dos pacientes estavam bem controlados (TTR médio: 78% ± 10%), com 1,6% apresentando grandes sangramentos na mediana do seguimento e custos médicos diretos por membro por ano (PMPY) de R$25.352 (± R$37.762). Pacientes com controle abaixo do ideal (69%) foram associados a 3,3 vezes mais sangramentos graves (5,3% vs. 1,6%; p <0,01) e custos 40% maiores (R$35.384 vs. R$25.352; p < 0,01). Conclusões: Mais de 60% dos pacientes estavam abaixo da meta desejada e os custos associados foram significativamente maiores nesta população.

Abstract Background: The safety and effectiveness of warfarin depend on anticoagulation control quality. Observational studies associate poor control with increased morbidity, mortality and healthcare costs. Objectives: To develop a profile of non-valvular atrial fibrillation (NVAF) patients treated with warfarin in a Brazilian private ambulatory and hospital setting, evaluate the quality of anticoagulation control, and its association with clinical and economic outcomes. Methods: This retrospective study, through a private health insurance dataset in Brazil, identified NVAF patients treated with warfarin between 01 MAY 2014 to 30 APRIL 2016, described their anticoagulation management, and quantified disease-related costs. Data on demographics, clinical history, concomitant medication and time in therapeutic range (TTR) of international normalized ratio (INR) values were retrieved. Patients were grouped into TTR quartiles, with good control defined as TTR ≥ 65% (Rosendaal method). Major bleeds and all-cause direct medical costs were calculated and compared between good and poor control subgroups. P-values < 0.05 were considered statistically significant. Results: The analysis included 1220 patients (median follow-up: 1.5 years; IQR: 0.5-2.0). On average, each patient received 0.95 monthly INR measurements (mean INR: 2.60 ± 0.88, with 26.1% of values < 2 and 24.8% > 3), (median TTR: 58%; IQR: 47-68%), (mean TTR: 56.6% ± 18.9%). Only 31% of patients were well-controlled (mean TTR: 78% ± 10%), with 1.6% having major bleeds within median follow-up, and direct medical costs per member per year (PMPY) of R$25,352(± R$ 37,762). Poorly controlled patients (69%) were associated with 3.3 times more major bleeds (5.3% vs. 1.6%; p < 0.01) and 40% higher costs (R$35,384 vs. R$25,352; p < 0.01). Conclusions: More than 60% of the patients were below the desired target and the associated costs were higher.

The coronavirus disease 2019 (COVID-19) is an emerging pandemic challenge. Acute respiratory distress syndrome (ARDS) in COVID-19 is characterized by a severe cytokine storm. Patients undergoing glucocorticoid (GC) replacement therapy for adrenal insufficiency (AI) represent a highly vulnerable group that could develop severe complications due to the SARS-CoV-2 infection. In this review, we highlight the strategies to avoid an adrenal crisis in patients with AI and COVID-19. Adrenal crisis is a medical emergency and an important cause of death. Once patients with AI present symptoms of COVID-19, the dose of GC replacement therapy should be immediately doubled. In the presence of any emergency warning signs or inability to administer oral GC doses, we recommend that patients should immediately seek Emergency services to evaluate COVID-19 symptoms and receive 100 mg hydrocortisone by intravenous injection, followed by 50 mg hydrocortisone intravenously every 6 h or 200 mg/day by continuous intravenous infusion.

OBJECTIVES: High-throughput sequencing of genomes, exomes, and disease-focused gene panels is becoming increasingly common for molecular diagnostics. However, identifying a single clinically relevant pathogenic variant among thousands of genetic polymorphisms is a challenging task. Publicly available genomic databases are useful resources to filter out common genetic variants present in the population and enable the identification of each disease-causing variant. Based on our experience applying these technologies at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP), São Paulo, Brazil, we recognized that the Brazilian population is not adequately represented in widely available genomic databases. METHODS: Here, we took advantage of our 5-year experience as a high-throughput sequencing core facility focused on individuals with putative genetic disorders to build a genomic database that may serve as a more accurate reference for our patient population: SELAdb. RESULTS/CONCLUSIONS: Currently, our database comprises a final cohort of 523 unrelated individuals, including patients or family members managed by different clinics of HCFMUSP. We compared SELAdb with other publicly available genomic databases and demonstrated that this population is very heterogeneous, largely resembling Latin American individuals of mixed origin, rather than individuals of pure European ancestry. Interestingly, exclusively through SELAdb, we identified a spectrum of known and potentially novel pathogenic variants in genes associated with highly penetrant Mendelian disorders, illustrating that pathogenic variants circulating in the Brazilian population that is treated in our clinics are underrepresented in other population databases. SELAdb is freely available for public consultation at: http://intranet.fm.usp.br/sela

RESUMO Objetivos: Herpes Zoster Oftálmico (HZO) é uma doença causada pelo vírus varicella-zoster que comumente afeta idosos ou doentes imunossuprimidos, com potencial para gerar graves comorbidades oculares, incluindo úlceras corneanas, uveíte, necrose retiniana e neuralgia pós-herpética. O objetivo deste estudo foi avaliar estes pacientes na forma aguda da doença e descrever seu perfil clínico e achados oftalmológicos. Métodos: Um estudo transversal foi realizado entre março de 2014 e outubro de 2015. Todos os pacientes consecutivos com o diagnóstico de HZO (na forma vesicular, pustulosa ou crostosa) foram incluídos e submetidos ao exame oftalmológico que incluiu ectoscopia, melhor acuidade visual corrigida, teste de sensibilidade corneana, biomicroscopia, tonometria de aplanação de Goldmann e fundoscopia. Resultados: Dezenove pacientes foram incluídos. A idade média foi de 71 anos. Dez (52,6%) pacientes relataram hipertensão arterial sistêmica e nove (47,3%) diabetes mellitus. A acuidade visual do olho acometido se encontrou abaixo do olho contra lateral em 57% dos casos, variando entre uma a seis linhas de visão. A pressão intraocular não variou na maioria dos casos em comparação com o olho contralateral. O sinal de Hutchinson estava presente em sete (36%) pacientes. A correlação entre este sinal e a presença tanto de reação de câmara anterior quanto de hipoestesia corneana foi positiva estatisticamente, com teste exato de Fisher de 0,009 e 0,029 respectivamente (p<0,05). Conclusão: Idosos com uma prevalência elevada de diabetes mellitus representaram o perfil clínico dos pacientes deste estudo. A correlação entre o sinal de Hutchinson e reação de câmara anterior, bem como daquele com hipoestesia corneana foi estatisticamente significativa. Não foi identificado nenhum caso de hipertensão ocular ou complicações de segmento posterior.

ABSTRACT Objective: Herpes Zoster Ophthalmicus (HZO) is caused by varicella-zoster virus (VZV) and commonly affects elderly or immunocompromised patients. It has the potential to generate severe complications such as corneal ulcers, uveitis, retinal necrosis and post herpetic neuralgia. This study aimed to evaluate patients at the acute onset of the disease and describe their clinical profile and ophthalmologic findings. Methods: A cross-sectional study was performed from March 2014 to October 2015. All consecutive patients with the diagnosis of acute HZO (at a vesicle, pustule or crust stage) were enrolled and submitted to an ophthalmologic exam that included ectoscopy, best corrected visual acuity, corneal sensitivity test, slit-lamp examination, Goldmann applanation tonometry and funduscopic examination. Results: Nineteen patients were included. The mean age was 71 years old, ranging from 52 to 88. Ten patients had high blood pressure (52.6%) and nine (47.3%) had diabetes. Visual acuity lowered in comparison to the fellow eye in eleven patients (57%), ranging from one to six lines of vision, due mostly to epithelial keratitis and ocular discharge. Intraocular pressure (IOP) did not varied in most cases compared to the fellow eye. Hutchinson's sign (HS) was present in seven (36%) patients. The correlation between HS and anterior chamber reaction as well as decreased corneal sensitivity was statistically significant with Fisher's test of 0.009 and 0.029 respectively (p<0.05). Conclusion: The clinical profile of our patients was elderly patients with a higher rate of diabetes. Correlation between Hutchinson's sign and anterior chamber reaction as well as decrease in corneal sensitivity was significant. High intraocular pressure or posterior segment complications were not found in any cases.