Introduction: The anterior cruciate ligament is one of the main ligaments of the knee, often more susceptible to injuries due to its central position and its vital role in stabilizing this joint. The strength of the quadriceps plays a crucial role, with impact absorption function, helping to reduce load. Objective: To evaluate the volume and strength of the quadriceps muscle before and after reconstruction of the anterior cruciate ligament of the knee, their correlation and which variables predict pre- and postoperative muscle strength. Method: Prospective cohort of 37 patients evaluated preoperatively and 4 months after the operation, using magnetic resonance imaging and isokinetic dynamometry. The measurements of the limb undergoing the operation were compared to the contralateral limb as a control. Result: The volume of the quadriceps muscle was 65.2+13.4cm3 before and 63.4+15.9 cm3 after, significantly lower in the control at both moments, with a reduction of 3.0cm3 (4.1%) in the pre and 7.8 cm3 post (12.0%). Muscle strength was 105.5+29.9N/m before and 100.9+28.6N/m after, significantly lower in the operated limb (126.4+28.2N/m and 129.6+27.6N /m, p<0.001). This reduction was similar in the 2 evaluation moments, on average of 17.5N/m (16.3%) in the pre and 22.8N/m (22.5%) in the post. The loss of strength was greater than the loss of muscle volume, with muscle volume and time of anterior cruciate ligament injury being the main determinants of muscle strength in the pre-op. The strength in the post was mainly determined by that in the pre. Conclusion: The loss of muscle strength was 4 times greater than the loss of volume pre-operatively and 2 times greater post-operatively, indicating the beginning of recovery 4 months post-operatively.

Introdução: O ligamento cruzado anterior é um dos principais ligamentos do joelho, frequentemente mais suscetível às lesões devido à sua posição central e seu papel vital na estabilização desta articulação. A força do quadríceps desempenha papel crucial, com função de absorção de impacto, auxiliando na redução de carga. Objetivo: Avaliar o volume e a força do músculo quadríceps antes e após a reconstrução do ligamento cruzado anterior do joelho, sua correlação e quais as variáveis preditivas da força muscular pré e pós-operatória. Método: Coorte prospectiva de 37 pacientes avaliados no pré-operatório e com 4 meses após a operação, por meio de ressonância magnética e dinamometria isocinética. As medidas do membro submetido à operação foram comparadas ao membro contralateral como controle. Resultado: O volume do músculo quadríceps foi de 65,2+13,4cm3 antes e de 63,4+15,9 cm3 após, significativamente menor no controle nos 2 momentos, com redução de 3,0cm3 (4,1%) no pré e 7,8 cm3 no pós (12,0%). A força muscular foi de 105,5+29,9N/m antes e de 100,9+28,6N/m após, significativamente menor no membro operado (126,4+28,2N/m e 129,6+27,6N/m, p<0,001). Esta redução foi semelhante nos 2 momentos de avaliação, em média de 17,5N/m (16,3%) no pré e de 22,8N/m (22,5%) no pós. A perda de força foi maior que a perda de volume muscular, sendo que o volume muscular e o tempo da lesão do ligamento cruzado anterior foram os principais determinantes da força muscular no pré. A força no pós foi determinada principalmente pela do pré. Conclusão: A perda de força muscular foi 4 vezes maior que a perda de volume no pré e 2 vezes maior no pós, indicando início da recuperação com 4 meses no pós-operatório.

Abstract Background: Primary cutaneous CD4+ small/medium-sized pleomorphic T-Cell lymphoproliferative disorder (PC-SMTLD) has been considered as a controversial dermatological disease that has been included in cutaneous T-cell lymphoma group, presenting most commonly as a solitary nodule and/or plaque with a specific and characteristic head and neck predilection. Due to the considerable overlap between PC-SMTLD and pseudolymphoma (PL), the differential diagnosis is often challenging. Methylation of DNA at position 5 of cytosine, and the subsequent reduction in intracellular 5-hydroxymethylcytosine (5-hmC) levels, is a key epigenetic event in several cancers, including systemic lymphomas. However, it has rarely been studied in cutaneous lymphomas. Objectives: The authors aimed to explore the role of differential 5-hmC immunostaining as a useful marker to distinguish PC-SMTLD from PL. Methods: Retrospective case series study with immunohistochemical and immunofluorescence analysis of 5-hmC was performed in PL and PC-SMTLD. Results: Significant decrease of 5-hmC nuclear staining was observed in PC-SMTLD when compared with PL (p<0.0001). By semi-quantitative grade integration, there were statistical differences in the final 5-hmC scores in the two study groups. The IF co-staining of 5-hmC with CD4 revealed a decrease of 5-hmC in CD4+ lymphocytes of PC-SMTLD. Study limitations: The small clinical sample size of the study. Conclusions: The immunorreactivity of 5-hmC in CD4+ lymphocytes was highly suggestive of a benign process as PL. Furthermore, the decrease of 5-hmC nuclear staining in PC-SMTLD indicated its lymphoproliferative status and helped to make the differential diagnosis with PL. © 2023 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

Resumo A ivermectina é um fármaco seguro e eficaz em seres humanos e é aprovado para uso em inúmeras infecções parasitárias há mais de 50 anos. Além disso, muitos estudos já evidenciaram sua atividade antiviral. A ivermectina é geralmente bem tolerada, sem indicação de toxicidade associada ao sistema nervoso central para doses até 10 vezes a dose mais alta, aprovada pelo FDA (Food and Drug Administration), de 200 µg/kg. Os resultados in vitro da ivermectina para redução da carga viral do SARS-CoV-2 são promissores e mostram que a Ivermectina mata o SARS-CoV-2 dentro de 48 horas. Uma hipótese de mecanismo de ação para esta droga é uma provável inibição da importação nuclear de proteínas virais mediada por IMPα / β1 como demonstrado para outros vírus de RNA. No entanto, estudos controlados e randomizados são necessários para comprovar sua eficácia na COVID-19 em humanos. Em um único estudo in vivo com resultados publicados, pacientes confirmadamente infectados por SARS-CoV-2 receberam pelo menos uma dose de ivermectina em qualquer momento durante a hospitalização. A utilização da ivermectina foi associada a menor mortalidade durante o tratamento com COVID-19, especialmente em pacientes que necessitaram de maior oxigênio inspirado ou suporte ventilatório. Adicionalmente, 81 estudos com o uso clínico da ivermectina em humanos estão sendo realizados em todo o mundo segundo o site ClinicalTrials.gov. Porém, nenhum destes teve seus dados publicados até o momento. No entanto, entidades privadas e públicas no Brasil vêm adotando este medicamento em seus protocolos como profilaxia e na fase inicial da doença. Além disto, a ivermectina é utilizada no tratamento em massa na prevenção da oncocercose e filariose linfática na África subsaariana há muitos anos. Surpreendentemente, esta região possui o menor índice de mortalidade proporcional entre os continentes, apesar dos números crescentes de contaminados divulgados pela Organização Mundial da Saúde.

Abstract Ivermectin is a safe and effective drug in humans and has been approved for use in numerous parasitic infections for over 50 years. In addition, many studies have already shown its antiviral activity. Ivermectin is generally well tolerated, with no indication of central nervous system-associated toxicity at doses up to 10 times the highest FDA-approved dose of 200 µg/kg. The in vitro results of ivermectin for reducing SARS-CoV-2 viral load are promising and show that Ivermectin kills SARS-CoV-2 within 48 hours. A hypothesized mechanism of action for this drug is a likely inhibition of IMPα/β1-mediated nuclear import of viral proteins as demonstrated for other RNA viruses. However, controlled and randomized studies are needed to prove its effectiveness in COVID-19 in humans. In a single in vivo study with published results, patients confirmed to be infected with SARS-CoV-2 received at least one dose of ivermectin at any time during hospitalization. The use of ivermectin was associated with lower mortality during treatment with COVID-19, especially in patients who required increased inspired oxygen or ventilatory support. Additionally, 81 studies with the clinical use of ivermectin in humans are being carried out worldwide according to ClinicalTrials.gov. However, none of these data has been published so far. However, private and public entities in Brazil have been adopting this drug in their protocols as prophylaxis and in the initial phase of the disease. In addition, ivermectin has been used in mass treatment to prevent onchocerciasis and lymphatic filariasis in sub-Saharan Africa for many years. Surprisingly, this region has the lowest proportional mortality rate among the continents, despite the increasing numbers of infected people released by the World Health Organization.

ABSTRACT Purpose: The purpose of this study was to evaluate the intraretinal layer thickness in the macular region and its correlation with the duration of uveitis and visual acuity in patients with Behçet uveitis. Methods: In this cross-sectional study, we included 93 eyes of 57 patients with Behçet uveitis and 100 eyes of 50 healthy individuals admitted to a tertiary center from January to September 2017. We performed macular measurements in all subjects via spectral domain-optical coherence tomography (SD-OCT) and divided the retina into layers using automated segmentation software on the SD-OCT device. We then compared layer thicknesses between the patient and control groups and evaluated the correlation between OCT parameters and the duration of uveitis and visual acuity in the patient group. Results: Our records show a mean age of 37.9 ± 10.8 (18-64) years and 37.7 ± 12.2 (21-61) years in the patient and control groups (p=0.821), respectively. Meanwhile, data reveal a mean duration of uveitis of 6.9 ± 4.7 (1-20) years. We found a reduction in the total outer layer thickness in the patient group (p<0.001). However, we did not find a statistically significant difference in the inner retinal layers except in the inner nuclear layer. The duration of uveitis negatively correlated with the outer retinal layer’s thickness (correlation coefficient = -0.250). On the other hand, visual acuity positively correlated with the central macular, the total inner layer, and the outer retinal layer thicknesses (correlation coefficients: 0.194, 0.154, and 0.364, respectively). However, the inner nuclear layer negatively correlated with visual acuity. Conclusions: Using retinal segmentation via SD-OCT for follow-ups can help estimate visual loss in patients with Behçet uveitis, which can cause significant changes in intraretinal layers in the macular region.

RESUMO Objetivo: Avaliar a espessura das camadas intraretinianas na região macular e sua relação com a duração da uveíte e acuidade visual em pacientes com uveíte de Behçet. Métodos: Este estudo transversal incluiu 93 olhos de 57 pacientes com uveíte de Behçet e 100 olhos de 50 indivíduos saudáveis que foram admitidos em um hospital terciário entre janeiro de 2017 e setembro de 2017. As medições maculares foram realizadas com tomografia de coerência óptica de domínio espectral (SD-OCT) em todos os pacientes. A retina foi dividida em camadas usando software de segmentação automatizado no dispositivo SD-OCT. As espessuras da camada foram comparadas entre os pacientes e os grupos controle. No grupo de pacientes, foi avaliada a correlação entre os parâmetros obtidos na OCT e a duração da uveíte e acuidade visual. Resultados: A média de idade foi de 37,9 ± 10,8 (18-64) no grupo de pacientes e 37,7 ± 12,2 (21-61) no grupo controle (p=0,821). A duração média da uveíte foi de 6,9 ± 4,7 (1-20) anos. A espessura total das camadas externas no grupo de pacientes foi reduzida (p<0,001). Uma diferença estatisticamente significativa não foi encontrada nas camadas internas da retina, exceto na camada nuclear interna. Uma correlação negativa foi detectada entre a duração da uveíte e a espessura da camada externa da retina (coeficiente de correlação = -0,250). Uma correlação positiva significativa foi detectada entre a acuidade visual e a espessura macular central bem como a espessura total das camadas internas e externas da retina (coeficientes de correlação 0,194; 0,154 e 0,364, respectivamente). A camada nuclear interna foi negativamente correlacionada com a acuidade visual. Conclusões: A uveíte de Behçet pode causar alterações significativas nas camadas intraretinianas na região macular. A segmentação da retina com SD-OCT pode ser útil para acompanhamentos e para estimar a perda visual em pacientes com uveíte de Behçet.

Resumen Este artículo consiste en una investigación de campo sobre las normas de género en un curso de Derecho en una universidad pública del Sur de Brasil, en que se investiga como las normas de género organizan las relaciones entre alumnas en el campo estudiado. La investigación, guiada por el postestructuralismo, tiene un enfoque cualitativo, con el objetivo exploratorio, y su punto central es las entrevistas realizadas durante 2021 en el campo de investigación mencionado. De las entrevistas surgieron declaraciones vinculadas a las relaciones de poder que involucran género, raza, corporalidad, edad, regionalismo, entre otros. Este estudio, buscando un análisis adecuado del material disponible a través de la interseccionalidad, se centra en categorías relacionadas con el género y la raza. También se basa en materiales grabados sobre el campo, puestos a disposición del público, así como en revisiones narrativas bibliográficas, uniendo el sesgo epistemológico con teóricos como Michel Foucault y Judith Butler, así como con referentes poscoloniales, como Lélia González, Enrique Dussel y Gayatri Spivak. De la investigación se desprende que las relaciones de poder establecidas conducen al mantenimiento del acceso, a la visibilidad y al reconocimiento académico a sujetos cuyos cuerpos y conductas encajan en el prescripciones del orden colonial.

Resumo O presente artigo consiste em pesquisa de campo sobre normas de gênero em curso de Direito de uma universidade pública no Sul do Brasil, em que se investiga como as normas de gênero organizam as relações entre discentes mulheres no campo estudado. A pesquisa, orientada pelo pós-estruturalismo, é de abordagem qualitativa, com objetivo exploratório, e tem como ponto nuclear entrevistas realizadas durante o ano de 2021 na área mencionada. Das entrevistas, emergiram enunciados atrelados a relações de poder que envolvem gênero, raça, corporalidades, idade, regionalismos, entre outros. Para este artigo, com inspiração na ferramenta da interseccionalidade, focam-se as categorias relacionadas ao gênero e à raça. Baseia-se, também, em materiais registrados do campo, disponibilizados publicamente, assim como em revisão bibliográfica narrativa, costurando o viés epistemológico com teóricos como Michel Foucault e Judith Butler, como também com referências pós-coloniais, como Lélia Gonzalez, Enrique Dussel e Gayatri Spivak. Da pesquisa, a partir da análise temática, notou-se que as relações de poder estabelecidas mantêm acessos, visibilidades e reconhecimentos acadêmicos a sujeitos cujos corpos e comportamentos se enquadrem nas prescrições da ordem colonial.

Abstract This article consists of field research on gender norms in a Law Undergraduate at a public university in the South of Brazil, in which it is investigated how gender norms organize the relationships between female students in the field studied. The research, guided by post-structuralism, has a qualitative approach, with an exploratory objective, and has as its core point interviews carried out during the year 2021 in the aforementioned area. From the interviews, statements linked to power relations involving gender, race, corporeality, age, regionalisms. For this study, inspired by the intersectionality tool, it focuses on categories related to gender and race. It is also based on publicly available registered materials from the field, as well as a narrative bibliographic review, stitching the epistemological bias with theorists such as Michel Foucault and Judith Butler, as well as with post-colonial references, such as Lélia Gonzalez, Enrique Dussel and Gayatri Spivak. From the research, from the thematic analysis, it was noticed that the established power relations maintain access, visibility and academic recognition to subjects whose bodies and behaviors fit the prescriptions of the colonial order.

Abstract In recent decades, there have been significant advances in the diagnosis of diffuse gliomas, driven by the integration of novel technologies. These advancements have deepened our understanding of tumor oncogenesis, enabling a more refined stratification of the biological behavior of these neoplasms. This progress culminated in the fifth edition of the WHO classification of central nervous system (CNS) tumors in 2021. This comprehensive review article aims to elucidate these advances within a multidisciplinary framework, contextualized within the backdrop of the new classification. This article will explore morphologic pathology and molecular/genetics techniques (immunohistochemistry, genetic sequencing, and methylation profiling), which are pivotal in diagnosis, besides the correlation of structural neuroimaging radiophenotypes to pathology and genetics. It briefly reviews the usefulness of tractography and functional neuroimaging in surgical planning. Additionally, the article addresses the value of other functional imaging techniques such as perfusion MRI, spectroscopy, and nuclear medicine in distinguishing tumor progression from treatment-related changes. Furthermore, it discusses the advantages of evolving diagnostic techniques in classifying these tumors, as well as their limitations in terms of availability and utilization. Moreover, the expanding domains of data processing, artificial intelligence, radiomics, and radiogenomics hold great promise and may soon exert a substantial influence on glioma diagnosis. These innovative technologies have the potential to revolutionize our approach to these tumors. Ultimately, this review underscores the fundamental importance of multidisciplinary collaboration in employing recent diagnostic advancements, thereby hoping to translate them into improved quality of life and extended survival for glioma patients.

Resumo Nas últimas décadas, houve avanços significativos no diagnóstico de gliomas difusos, impulsionados pela integração de novas tecnologias. Esses avanços aprofundaram nossa compreensão da oncogênese tumoral, permitindo uma estratificação mais refinada do comportamento biológico dessas neoplasias. Esse progresso culminou na quinta edição da classificação da OMS de tumores do sistema nervoso central (SNC) em 2021. Esta revisão abrangente tem como objetivo elucidar esses avanços de forma multidisciplinar, no contexto da nova classificação. Este artigo irá explorar a patologia morfológica e as técnicas moleculares/genéticas (imuno-histoquímica, sequenciamento genético e perfil de metilação), que são fundamentais no diagnóstico, além da correlação dos radiofenótipos da neuroimagem estrutural com a patologia e a genética. Aborda sucintamente a utilidade da tractografia e da neuroimagem funcional no planejamento cirúrgico. Destacaremos o valor de outras técnicas de imagem funcional, como ressonância magnética de perfusão, espectroscopia e medicina nuclear, na distinção entre a progressão do tumor e as alterações relacionadas ao tratamento. Discutiremos as vantagens das diferentes técnicas de diagnóstico na classificação desses tumores, bem como suas limitações em termos de disponibilidade e utilização. Além disso, os crescentes avanços no processamento de dados, inteligência artificial, radiômica e radiogenômica têm grande potencial e podem em breve exercer uma influência substancial no diagnóstico de gliomas. Essas tecnologias inovadoras têm o potencial de revolucionar nossa abordagem a esses tumores. Em última análise, esta revisão destaca a importância fundamental da colaboração multidisciplinar na utilização dos recentes avanços diagnósticos, com a esperança de traduzi-los em uma melhor qualidade de vida e uma maior sobrevida.

ABSTRACT The climatic cycles of the Pleistocene affected the distribution of the vegetation of different bio-mes, determining the distribution and evolution of the associated fauna. Many studies of Atlantic Forest (AF) organisms suggest that the Pleistocene glacial and interglacial cycles have produced demographically stable populations in the forest’s central region and unstable populations in its southern regions (known as the Car-naval-Moritz model). We studied the phylogeographic structure of an AF passerine, the Black-goggled Tanager (Trichothraupis melanops, Thraupidae) and evaluated questions related to the history of the AF. We analyzed three independent genes, two nuclear and one mitochondrial, using population genetic methods based on summary statistics and traditional phylogeographic methods. Our results suggest that T. melanops shares phylogeographic features with other AF taxa. Even though an effective population size gradient was found between the central and southern populations, which is in agreement with the results of other phylogeographic studies and the forest refugia model (the Carnaval-Moritz model), there is no evidence of a gradient of genetic diversity. In addition, we have found that T. melanops populations show the demographic dynamics expected according to the Carnaval-Moritz model: the inland-southern population was found to be the one with the greatest signs of recent demographic expansion, compared to the central and coastal-southern populations. Although this species is ecologically generalist and not very sensitive to forest fragmentation and degradation, it has been impacted by the historical dynamism of the AF.

RESUMEN Los ciclos climáticos del Pleistoceno afectaron la distribución de la vegetación de diferentes bio-mas, condicionando la distribución y evolución de la fauna asociada. Muchos estudios sobre organismos de la Selva Atlántica (SA) sugieren que los ciclos glaciales e interglaciales del Pleistoceno han producido poblaciones demográficamente estables en la región central de la selva y poblaciones inestables en sus regiones del sur (conocido como modelo Carnaval-Moritz). Estudiamos la estructura filogeográfica de un paseriforme que se distribuye en la SA, el Frutero de Anteojos Negros (Trichothraupis melanops, Thraupidae), y evaluamos preguntas relacionadas con la historia de la SA. Analizamos tres genes independientes, dos nucleares y uno mitocondri Editora Asociada: Bettina Mahler al, utilizando métodos de genética de poblaciones basados en estadísticas sumarias y métodos filogeográficos tradicionales. Nuestros resultados sugieren que T. melanops comparte características filogeográficas con otros taxones de la SA. Si bien se encontró un gradiente de tamaño poblacional efectivo entre las poblaciones del centro y del sur, lo que concuerda con los resultados de otros estudios filogeográficos y el modelo de refugios (el modelo Carnaval-Moritz), no hay evidencia de un gradiente de diversidad genética. Además, hemos encontrado que las poblaciones de T. melanops presentan la dinámica demográfica esperada por el modelo Carnaval-Moritz: la población del centro-sur resultó ser la que presenta mayores signos de expansión demográfica reciente, en comparación con las poblaciones central y de la costa sur. Aunque esta especie es ecológicamente generalista y poco sensible a la fragmentación y degradación forestal, ha sido impactada por el dinamismo histórico de la Selva Atlántica.

Abstract Autoimmune encephalitis is an immune-mediated disorder that affects different areas of the brain parenchyma, often involving deep gray matter or the cortex, with or without involvement of white matter, meninges, or spinal cord. It is frequently associated with autoimmune or paraneoplastic diseases and is a diagnostic challenge. We report the case of a 55-year-old woman with history of Sjögren's syndrome who presented to the emergency department with headache and episodes of confusion. Cerebrospinal fluid (CSF) analysis showed leukocytosis with neutrophilia. Brain MRI revealed multiple restricted diffusion lesions with hyperintense signal on T2 and FLAIR sequences, predominantly in the bilateral occipital region, right cerebellar hemisphere, and right parietal region. Infections and neoplasms were ruled out. The panel of antibodies for autoimmune encephalitis, including Aquaporin-4 and anti-MOG in CSF, was negative. She received intravenous methylprednisolone, leading to symptom improvement.

Resumen La encefalitis autoinmune es un trastorno inmunomediado que compromete distintos territorios del parénquima cerebral, involucrando frecuentemente la materia gris profunda o la corteza, con o sin compromiso de la materia blanca, meninges o médula espinal. Se asocia frecuentemente con enfermedades autoinmunes o paraneoplásicas, y constituye un reto diagnóstico. Reportamos el caso de una mujer de 55 años con antecedente de síndrome de Sjögren que consultó a Emergencias por cefalea y confusión. El líquido cefalorraquídeo (LCR) presentaba leucocitosis con neutrofilia. En la resonancia magnética nuclear (RMN) cerebral se evidenciaron múltiples imágenes de comportamiento restrictivo, de señal hiperintensa en T2 y FLAIR, a predominio córtico-subcortical a nivel occipital bilateral, hemisferio cerebeloso derecho y parietal derecho. Se descartaron infecciones y neoplasias. El panel de anticuerpos para encefalitis autoinmune aquaporina-4 y anti-MOG en LCR fue negativo. Recibió metilprednisolona endovenosa con mejoría progresiva de los síntomas.

Abstract When he took office after the electoral campaign, Alfonsín tried to send a positive signal to the United States, declaring that the country identified, at least from a cultural point of view, with the West. The White House should not fear, then, that the UCR president may display a high profile in the Non-Aligned Movement. This did not imply subservience to Washington, since differences persisted, for example, due to his position as regards nuclear non-proliferation, the Central America’s crisis and the foreign debt. The greatest bilateral convergence began in September 1984, during the first presidential meeting between Alfonsín and Reagan. In this article we will analyze the different stages of the complex relationship between the two presidents, their political differences and the Argentine economic needs.

Resumen Cuando asumió, luego de la campaña electoral, Alfonsín intentó dar seguridades a Estados Unidos, declarando que el país se identificaba, al menos desde el punto de vista cultural, con Occidente. La Casa Blanca no debía temer, entonces, que el presidente radical desplegara un alto perfil en el Movimiento de Países No Alineados. Esto no implicaba subordinarse a Washington, ya que persistían, entre otras, diferencias por la no proliferación nuclear, la crisis en América Central y la deuda externa. La mayor convergencia bilateral se inició en septiembre de 1984, en ocasión del primer encuentro presidencial entre Alfonsín y Reagan. En este artículo analizamos las distintas etapas de la compleja relación entre los presidentes, sus diferencias políticas y las necesidades económicas argentinas.

ABSTRACT The Northeastern Pacific (NEP) population of white sharks (Carcharodon carcharias) is genetically distinct from the rest of the world. This uniqueness results from adult fidelity to central California and Guadalupe Island aggregations sites. The strong mitochondrial genetic structure between the white sharks of central California and Guadalupe Island is also present, which indicates female philopatry. To date, few studies using nuclear DNA have found evidence of genetic patterns in the NEP white shark population, which could indicate that these sharks exhibit sex-biased dispersal. In this study, we evaluated the genetic structure, connectivity, and genetic diversity of NEP white sharks using samples from the southern California Bight (SCB), Baja California (including Sebastian Vizcaino Bay), the Gulf of California, and Guadalupe Island (GI) using nDNA (i.e. microsatellite loci). A total of five loci were successfully genotyped in 54 individuals. The patterns found in this study indicated low levels of genetic diversity among all localities (observed heterozygosity: Ho = 0.47), likely due to a founder effect. A slight genetic structure was present for NEP localities in this study (FST = 0.045, P = 0.0001), mainly identified between the SCB and GI locations. A sibship assignment analysis indicated low and moderate probabilities of full- and half-siblings between white shark juveniles from coastal areas, suggesting a high degree of connectivity between nursery areas in the NEP. Our results suggest that juveniles can mask the genetic structure in coastal zones.

ABSTRACT Between 1946 and 1948, Brazilian physicist César Lattes played a central role in the experimental observation of mesons. After earning his bachelor’s degree from the University of São Paulo, Lattes developed specific skills sets in nuclear physics, and later handled instruments at laboratories associated with the University of Bristol and the University of California, Berkeley. This article analyzes records produced by scientists from these laboratories during their studies of nuclei, and compares their practices and values. It gives special attention to the non-verbal experimental knowledge that Lattes developed and promoted, which was essential for creating instrumental sets and identifying visual evidence of the existence of mesons. Throughout this work, Lattes adapted easily to laboratories and extracted the most he possibly could from available instruments and theories.

RESUMEN Entre 1946 y 1948, el físico brasileño César Lattes tuvo una participación destacada en la observación experimental de los Mesones. Manipulando instrumentos disponibles en los laboratorios de las Universidades de Bristol y de Berkeley, después de graduarse en la Universidad de São Paul, Lattes tuvo contacto con estilos de pensamiento distintos, de los cuales se apropió de habilidades específicas en la Física nuclear. Analizaré inscripciones producidas por científicos de estos laboratorios en sus estudios sobre el núcleo, comparando sus prácticas y valores. Daré atención al saber no verbal que Lattes desarrolló y fue portador, especial para pensar acuerdos instrumentales e identificar evidencias visuales de la existencia de los Mesones. Se evidencia a lo largo del trabajo, su fácil adaptación a laboratorios y su sensibilidad para extraer de los instrumentos y teorías disponibles lo mejor que podían dar.

RESUMO Entre 1946 e 1948, o físico brasileiro César Lattes teve participação central na observação experimental dos mésons. Manuseando instrumentos disponíveis nos laboratórios das Universidades de Bristol e de Berkeley, após se formar na Universidade de São Paulo, Lattes teve contato com estilos de pensamento distintos, dos quais apropriou habilidades específicas na Física nuclear. Analisarei inscrições produzidas por cientistas desses laboratórios em seus estudos sobre o núcleo, comparando suas práticas e valores. Dedicarei atenção ao saber não verbal que Lattes desenvolveu e foi portador, essencial para pensar arranjos instrumentais e identificar evidências visuais da existência dos mésons. Evidencia-se, ao longo do trabalho, sua fácil adaptação a laboratórios e sua sensibilidade para extrair dos instrumentos e teorias disponíveis o melhor que podiam dar.

ABSTRACT Interstitial keratitis is an inflammation of the corneal stroma without epithelium or endothelium involvement. The underlying causes are mostly infectious or immune mediated. Brazil has one of the highest incidence rates of tuberculosis in the world. Tuberculosis is considered one of the causes of interstitial keratitis. Malnutrition and anemia are risk factors of the disseminated disease. This is a case report of a 10-year-old child who presented with decreased visual acuity and a clinical diagnosis of bilateral interstitial keratitis and sclero-uveitis. The patient had been treated with topical steroids with partial improvement. Examinations revealed severe iron deficiency anemia, negative serologies for human immunodeficiency virus and syphilis, positivity for cytomegalovirus- and herpes simplex-specific IgG, and purified protein derivative of 17 mm. During the follow-up, the patient presented with tonic-clonic seizures, and magnetic resonance imaging findings suggested a central nervous system tuberculoma. Interstitial keratitis improvement was observed after specific tuberculosis treatment. This is the first case report describing the association of interstitial keratitis and central nervous system tuberculoma.

RESUMO A ceratite intersticial é uma inflamação do estroma corneano sem envolvimento epitelial ou endotelial causada principalmente por doenças infecciosas e imunomediadas. O Brasil tem altas taxas de tuberculose que deve ser lembrada como causa de ceratite intersticial. Desnutrição e anemia são fatores de risco da forma disseminada da tuberculose. Este é um relato de uma criança de 10 anos com redução de acuidade visual e diagnóstico clínico de ceratite intersticial bilateral e esclerouveíte. O paciente obteve melhora parcial da ceratite com corticoide tópico. Exames laboratoriais mostraram anemia ferropriva grave, sorologias negativas para HIV e sífilis; IgM negativo e IgG positivo para citomegalovírus e herpes simplex e PPD positivo (17 mm). Ele evoluiu com crises tônico-clônicas e a ressonância nuclear magnética revelou tuberculoma do sistema nervoso central. A melhora da ceratite intersticial foi observada após tratamento para tuberculose. Este é o primeiro caso que descreve a associação de ceratite intersticial e tuberculoma do sistema nervoso central.

Abstract Background Alpha-kinase 1 (ALPK1) is a master regulator in inflammation and has been proved to promote renal fibrosis by promoting the production of IL-1β in diabetic nephropathy (DN) mice. Pyroptosis is involved in high glucose (HG)-induced tubular cells injury, characterized by activation of Gasdermin D (GSDMD) and the release of IL-1β and IL-18, resulting in inflammatory injury in DN. It is reasonable to assume that ALPK1 is involved in pyroptosis-related tubular injury in DN. However, the mechanism remains poorly defined. Methods Immunohistochemistry (IHC) staining was performed to detect the expression of pyroptosis- and fibrosis-related proteins in renal sections of DN patients and DN mice. DN models were induced through injection of streptozotocin combined with a high-fat diet. Protein levels of ALPK1, NF-κB, Caspase-1, GSDMD, IL-1β, IL-18 and α-SMA were detected by Western blot. HK-2 cells treated with high-glucose (HG) served as an in vitro model. ALPK1 small interfering RNA (siRNA) was transfected into HK-2 cells to down-regulate ALPK1. The pyroptosis rates were determined by flow cytometry. The concentrations of IL-1β and IL-18 were evaluated by ELISA kits. Immunofluorescence staining was used to observe translocation of NF-κB and GSDMD. Results The heat map of differentially expressed genes showed that ALPK1, Caspase-1 and GSDMD were upregulated in the DN group. The expression levels of ALPK1, Caspase-1, GSDMD and CD68 were increased in renal biopsy tissues of DN patients by IHC. ALPK1expression and CD68+ macrophages were positively correlated with tubular injury in DN patients. Western blot analysis showed increased expressions of ALPK1, phospho-NF-κB P65, GSDMD-NT, and IL-1β in renal tissues of DN mice and HK-2 cells, accompanied with increased renal fibrosis-related proteins (FN, α-SMA) and macrophages infiltration in interstitial areas. Inhibition of ALPK1 attenuated HG-induced upregulation expressions of NF-κB, pyroptosis-related proteins Caspase-1, GSDMD-NT, IL-1β, IL-18, α-SMA, and pyroptosis level in HK-2 cells. Also, the intensity and nuclear translocation of NF-κB and membranous translocation of GSDMD were ameliorated in HG-treated HK-2 cells after treatment with ALPK1 siRNA. Conclusions Our data suggest that ALPK1/NF-κB pathway initiated canonical caspase-1-GSDMD pyroptosis pathway, resulting in tubular injury and interstitial inflammation of DN.

ABSTRACT Purpose: To evaluate whether baseline spectral-domain optical coherence tomography characteristics of intraretinal cystoid spaces predict visual outcomes in patients receiving intravitreal antivascular endothelial growth factor injection therapy (bevacizumab 1.25mg/0.05ml) for diabetic cystoid macular edema. Methods: The relationship between the properties of the cystoid spaces before injection and anatomic and functional results after injection were investigated in patients who received three consecutive intravitreal bevacizumab injections for cystoid macular edema. The best-corrected visual acuity for functional success and central subfield thickness for anatomical success were evaluated. The relationship of the location of the cystoid spaces with the integrity of photoreceptors and inner retinal layers was also evaluated. Results: In 36 eyes of 36 patients, the mean best-corrected visual acuity significantly improved (p=0.002), and mean central subfield thickness decreased after injections (p=0.003). The improvement in best-corrected visual acuity was limited in eyes with outer nuclear layer cysts (p=0.045). Intracystic reflectivity was higher in eyes that poor best-corrected visual acuity than in eyes with successful visual outcomes (p=0.028). The disrupted ellipsoid zone was present in 13 (59.0%) of 22 eyes with outer nuclear layer cysts, whereas in only 1 of 14 eyes (7.1%) without outer nuclear layer cysts (p=0.009). Disorganization of retinal inner layers was present in 15 of 22 (68.1%) eyes with outer nuclear layer cysts, whereas only 2 of 14 (14.2%) without outer nuclear layer cysts had disorganization of retinal inner layers (p=0.013). Conclusion: Characteristics of intraretinal cystoid spaces may predict prognosis in patients with diabetic cystoid macular edema, and visual gain may be limited in the eyes with outer nuclear layer cysts.

RESUMO Objetivo: Avaliar se as características da tomografia de coerência óptica de domínio espectral dos espaços cistoides intraretinianos prevêem resultados visuais em pacientes que recebem terapia de injeção intravítrea com fator de crescimento endotelial antivascular (bevacizumab 1,25 mg/0,05 ml) para edema macular cistoide diabético. Métodos: A relação entre as propriedades dos espaços cistoides antes da injeção e os resultados anatômicos e funcionais após a injeção foi investigada em pacientes que receberam três injeções intravítreas para edema macular cistoide. A melhor acuidade visual corrigida para a melhora funcional e a espessura do subcampo central para a melhora anatômica foram avaliadas. Além disso, foi avaliada a relação da localização dos espaços cistoides com a integridade dos fotorreceptores e camadas internas da retina. Resultados: Em 36 olhos de 36 pacientes, a melhor acuidade visual corrigida foi significativamente aprimorada (p=0,002), e a espessura média do subcampo central foi diminuída após injeções (p=0,003). O aprimoramento da melhor acuidade visual corrigida foi limitado nos olhos com cistos na camada nuclear externa (p=0,045). A reflexividade intracística foi maior nos olhos que falharam na melhor acuidade visual corrigida do que nos olhos com resultados visuais bem-sucedidos (p=0,028). A zona elipsoide interrompida esteve presente em 13 (59,0%) de 22 olhos com cistos na camada nuclear externa, e em apenas 1 de 14 olhos (7,1%) sem cistos na camada nuclear externa (p=0,009). A desorganização das camadas internas da retina esteve presente em 15 dos 22 olhos (68,1%) com cistos na camada nuclear externa, enquanto apenas 2 em 14 olhos (14,2%) sem cistos na camada nuclear externa tiveram desorganização das camadas internas da retina (p=0,013). Conclusão: Características dos espaços cistoides intrarretinianos podem prever prognóstico em pacientes com edema macular cistoide diabético e ganho visual pode ser limitado nos olhos com cistos na camada nuclear externa.

ABSTRACT Purpose: Over-activation of nuclear factor kappa B (NF-κB) was proven to be involved in the pathogenesis of preeclampsia. However, its regulation mechanism is not clear yet. This paper explored the role of WD repeat domain 5 (WDR5) in the development of late-onset preeclampsia and its relationship with NF-κB. Methods: WDR5 expression was detected in normal placentas and placentas from late-onset preeclampsia patients. CCK-8 and colony formation assays were conducted to appraise the proliferative ability of trophoblast. Migration and invasion were observed by wound healing and transwell assays. The interaction between WDR5 and NF-κB inhibitor I-kappa-B-alpha (IkBa) was verified by Co-immunoprecipitation analysis. Immunofluorescence was used to analyze the activation of NF-κB. Finally, we tested the role of WDR5 using the mice late-onset preeclampsia model. Results: WDR5 was highly expressed in the placentas of late-onset preeclampsia patients. WDR5 overexpression suppressed cell proliferation, migration, and invasion in trophoblast. WDR5 could interact with IkBa to activate NF-κB. Knockdown of NF-κB counteracted the anti-proliferative and anti-metastatic effects of WDR5 overexpression in trophoblast. In-vivo studies suggested that targeting WDR5 combated late-onset preeclampsia development. Conclusions: Our finding provides new insights into the role of WDR5 in late-onset preeclampsia development.