Evaluation of glial tumors: correlation between magnetic resonance imaging and histopathological analysis.

Objective: To determine the correlation of conventional and diffusion-weighted imaging findings on magnetic resonance imaging (MRI) of the brain, based on Visually AcceSAble Rembrandt Images (VASARI) criteria, with the histopathological grading of gliomas: low-grade or high-grade. Materials and Methods: Preoperative MRI scans of 178 patients with brain gliomas and pathological confirmation were rated by two neuroradiologists for tumor size, location, and tumor morphology, using a standardized imaging feature set based on the VASARI criteria. Results: In the univariate analysis, more than half of the MRI characteristics evaluated showed a significant association with the tumor grade. The characteristics most significantly associated with the tumor grade were hemorrhage; restricted diffusion; pial invasion; enhancement; and a non-contrast-enhancing tumor crossing the midline. In a multivariable regression model, the presence of enhancement and hemorrhage maintained a significant association with high tumor grade. The absence of contrast enhancement and restricted diffusion were associated with the presence of an isocitrate dehydrogenase gene mutation. Conclusion: Our data illustrate that VASARI MRI features, especially intratumoral hemorrhage, contrast enhancement, and multicentricity, correlate strongly with glial tumor grade.

Objetivo: Determinar a correlação dos achados de imagem convencional e de difusão na ressonância magnética (RM) do encéfalo, com base nos critérios Visually AcceSAble Rembrandt Images (VASARI), com a classificação histopatológica de gliomas: gliomas de baixo grau e gliomas de alto grau. Materiais e Métodos: Imagens de RM pré-cirúrgicas de 178 pacientes com gliomas cerebrais e confirmação patológica foram avaliadas por dois neurorradiologistas quanto ao tamanho, localização e morfologia do tumor usando um padrão de imagem baseado nos critérios VASARI. Resultados: Na análise univariada, mais da metade das características avaliadas apresentou associação significativa com o grau do tumor. Hemorragia, restrição à difusão, invasão pial, realce e tumor sem realce cruzando a linha média foram as características com associação mais significativa. No modelo de regressão multivariada, a presença de realce e hemorragia manteve associação significativa com tumores de alto grau. A ausência de realce pelo meio de contraste e a restrição da difusão foram associados à presença da mutação do gene isocitrato desidrogenase. Conclusão: Nossos dados ilustram que as características de RM do VASARI, especialmente hemorragia intratumoral, presença de realce de contraste e multicentricidade, forneceram uma correlação importante com o grau da neoplasia glial.

A rare cause of postpartum seizure: Cerebral tuberculoma.

Tuberculomas are rare and a life-threatening condition. Diagnosis followed by appropriate treatment can lead to complete resolution of the disease. A suggestive imaging study in an appropriate clinical setting can lead to the diagnosis. We describe a case of a postpartum woman with a headache and seizure in which eclampsia was the initial suspicion. Imaging exams demonstrated a solitary expansile lesion in the left parietal lobe suspicious of neoplasia. A biopsy, instead, confirmed a tuberculoma. In addition to eclampsia, many other differential diagnoses are possible in the context of seizures in pregnant and peripartum patients, including central nervous system tuberculosis. Brain imaging studies can be crucial in the diagnostic process.

Mitochondrial superoxide dismutase Sod2 suppresses nuclear genome instability during oxidative stress.

Oxidative stress can damage DNA and thereby contribute to genome instability. To avoid an imbalance or overaccumulation of reactive oxygen species (ROS), cells are equipped with antioxidant enzymes that scavenge excess ROS. Cells lacking the RecQ-family DNA helicase Sgs1, which contributes to homology-dependent DNA break repair and chromosome stability, are known to accumulate ROS, but the origin and consequences of this oxidative stress phenotype are not fully understood. Here, we show that the sgs1 mutant exhibits elevated mitochondrial superoxide, increased mitochondrial mass, and accumulation of recombinogenic DNA lesions that can be suppressed by antioxidants. Increased mitochondrial mass in the sgs1Δ mutant is accompanied by increased mitochondrial branching, which was also inducible in wildtype cells by replication stress. Superoxide dismutase Sod2 genetically interacts with Sgs1 in the suppression of nuclear chromosomal rearrangements under paraquat (PQ)-induced oxidative stress. PQ-induced chromosome rearrangements in the absence of Sod2 are promoted by Rad51 recombinase and the polymerase subunit Pol32. Finally, the dependence of chromosomal rearrangements on the Rev1/Pol ζ mutasome suggests that under oxidative stress successful DNA synthesis during DNA break repair depends on translesion DNA synthesis.

Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain.

Crossing the blood-brain barrier in primates is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust, non-invasive gene delivery from the bloodstream to the brain. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates. Here we report on AAV.CAP-Mac, an engineered variant identified by screening in adult marmosets and newborn macaques, which has improved delivery efficiency in the brains of multiple non-human primate species: marmoset, rhesus macaque and green monkey. CAP-Mac is neuron biased in infant Old World primates, exhibits broad tropism in adult rhesus macaques and is vasculature biased in adult marmosets. We demonstrate applications of a single, intravenous dose of CAP-Mac to deliver functional GCaMP for ex vivo calcium imaging across multiple brain areas, or a cocktail of fluorescent reporters for Brainbow-like labelling throughout the macaque brain, circumventing the need for germline manipulations in Old World primates. As such, CAP-Mac is shown to have potential for non-invasive systemic gene transfer in the brains of non-human primates.

Advances in AAV technology for delivering genetically encoded cargo to the nonhuman primate nervous system.

Modern neuroscience approaches including optogenetics, calcium imaging, and other genetic manipulations have facilitated our ability to dissect specific circuits in rodent models to study their role in neurological disease. These approaches regularly use viral vectors to deliver genetic cargo (e.g., opsins) to specific tissues and genetically-engineered rodents to achieve cell-type specificity. However, the translatability of these rodent models, cross-species validation of identified targets, and translational efficacy of potential therapeutics in larger animal models like nonhuman primates remains difficult due to the lack of efficient primate viral vectors. A refined understanding of the nonhuman primate nervous system promises to deliver insights that can guide the development of treatments for neurological and neurodegenerative diseases. Here, we outline recent advances in the development of adeno-associated viral vectors for optimized use in nonhuman primates. These tools promise to help open new avenues for study in translational neuroscience and further our understanding of the primate brain.

Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates.

Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial-specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. We apply this approach to Hevin knockout mice, where AAV-X1-mediated ectopic expression of the synaptogenic protein Sparcl1/Hevin in brain endothelial cells rescued synaptic deficits.

Intravenous functional gene transfer throughout the brain of non-human primates using AAV.

Adeno-associated viruses (AAVs) promise robust gene delivery to the brain through non-invasive, intravenous delivery. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates (NHPs). Here we describe AAV.CAP-Mac, an engineered variant identified by screening in adult marmosets and newborn macaques with improved efficiency in the brain of multiple NHP species: marmoset, rhesus macaque, and green monkey. CAP-Mac is neuron-biased in infant Old World primates, exhibits broad tropism in adult rhesus macaques, and is vasculature-biased in adult marmosets. We demonstrate applications of a single, intravenous dose of CAP-Mac to deliver (1) functional GCaMP for ex vivo calcium imaging across multiple brain areas, and (2) a cocktail of fluorescent reporters for Brainbow-like labeling throughout the macaque brain, circumventing the need for germline manipulations in Old World primates. Given its capabilities for systemic gene transfer in NHPs, CAP-Mac promises to help unlock non-invasive access to the brain.

RTEL1 and MCM10 overcome topological stress during vertebrate replication termination.

Topological stress can cause converging replication forks to stall during termination of vertebrate DNA synthesis. However, replication forks ultimately overcome fork stalling, suggesting that alternative mechanisms of termination exist. Using proteomics in Xenopus egg extracts, we show that the helicase RTEL1 and the replisome protein MCM10 are highly enriched on chromatin during fork convergence and are crucially important for fork convergence under conditions of topological stress. RTEL1 and MCM10 cooperate to promote fork convergence and do not impact topoisomerase activity but do promote fork progression through a replication barrier. Thus, RTEL1 and MCM10 play a general role in promoting progression of stalled forks, including when forks stall during termination. Our data reveal an alternate mechanism of termination involving RTEL1 and MCM10 that can be used to complete DNA synthesis under conditions of topological stress.

Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates.

Delivering genes to and across the brain vasculature efficiently and specifically across species remains a critical challenge for addressing neurological diseases. We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds and rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and ex vivo human brain slices although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. Vasculature-secreted Hevin (a synaptogenic protein) rescued synaptic deficits in a mouse model.

A review of mental health disparities during COVID-19: Evidence, mechanisms, and policy recommendations for promoting societal resilience.

Social and economic inequality are chronic stressors that continually erode the mental and physical health of marginalized groups, undermining overall societal resilience. In this comprehensive review, we synthesize evidence of greater increases in mental health symptoms during the COVID-19 pandemic among socially or economically marginalized groups in the United States, including (a) people who are low income or experiencing homelessness, (b) racial and ethnic minorities, (c) women and lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ+) communities, (d) immigrants and migrants, (e) children and people with a history of childhood adversity, and (f) the socially isolated and lonely. Based on this evidence, we propose that reducing social and economic inequality would promote population mental health and societal resilience to future crises. Specifically, we propose concrete, actionable recommendations for policy, intervention, and practice that would bolster five "pillars" of societal resilience: (1) economic safety and equity, (2) accessible healthcare, including mental health services, (3) combating racial injustice and promoting respect for diversity, equity, and inclusion, (4) child and family protection services, and (5) social cohesion. Although the recent pandemic exposed and accentuated steep inequalities within our society, efforts to rebuild offer the opportunity to re-envision societal resilience and policy to reduce multiple forms of inequality for our collective benefit.

Engineered AAVs for non-invasive gene delivery to rodent and non-human primate nervous systems.

Gene therapy offers great promise in addressing neuropathologies associated with the central and peripheral nervous systems (CNS and PNS). However, genetic access remains difficult, reflecting the critical need for the development of effective and non-invasive gene delivery vectors across species. To that end, we evolved adeno-associated virus serotype 9 (AAV9) capsid in mice and validated two capsids, AAV-MaCPNS1 and AAV-MaCPNS2, across rodent species (mice and rats) and non-human primate (NHP) species (marmosets and rhesus macaques). Intravenous administration of either AAV efficiently transduced the PNS in rodents and both the PNS and CNS in NHPs. Furthermore, we used AAV-MaCPNS1 in mice to systemically deliver the following: (1) the neuronal sensor jGCaMP8s to record calcium signal dynamics in nodose ganglia and (2) the neuronal actuator DREADD to dorsal root ganglia to mediate pain. This conclusively demonstrates the translatability of these two systemic AAVs across four species and their functional utility through proof-of-concept studies in mice.

Central nervous system infection: imaging findings suggestive of a fungus as the cause.

Fungal infections of the central nervous system (CNS) are rare. However, because of the increase in the number of immunocompromised individuals, they have been gaining prominence in the differential diagnosis of CNS infections. Imaging techniques are sensitive for detecting and localizing an abnormality, in many cases allowing the origin of a lesion to be categorized as infectious, inflammatory, neoplastic, or vascular. This essay illustrates the magnetic resonance imaging and computed tomography findings of the most common fungal infections of the CNS, based on the experience of the Radiology Department of the Hospital de Clínicas de Porto Alegre, in the city of Porto Alegre, RS, Brazil.

As infecções fúngicas do sistema nervoso central (SNC) são raras, entretanto, com o aumento no número de indivíduos imunocomprometidos elas têm ganhado destaque no diagnóstico diferencial de infecções no SNC. As atuais técnicas de imagem são sensíveis para detectar uma anormalidade, localizá-la, e em muitos casos categorizar a lesão como de origem infecciosa e/ou inflamatória, neoplásica ou vascular. Este ensaio ilustra os achados de ressonância magnética e tomografia computadorizada mais comuns nas infecções fúngicas do SNC baseadas na experiência do Serviço de Radiologia do Hospital de Clínicas de Porto Alegre.

Central nervous system infection: imaging findings suggestive of a fungus as the cause / Infecção do sistema nervoso central: os achados de imagem sugestivos de fungo como causa

Abstract Fungal infections of the central nervous system (CNS) are rare. However, because of the increase in the number of immunocompromised individuals, they have been gaining prominence in the differential diagnosis of CNS infections. Imaging techniques are sensitive for detecting and localizing an abnormality, in many cases allowing the origin of a lesion to be categorized as infectious, inflammatory, neoplastic, or vascular. This essay illustrates the magnetic resonance imaging and computed tomography findings of the most common fungal infections of the CNS, based on the experience of the Radiology Department of the Hospital de Clínicas de Porto Alegre, in the city of Porto Alegre, RS, Brazil.

Resumo As infecções fúngicas do sistema nervoso central (SNC) são raras, entretanto, com o aumento no número de indivíduos imunocomprometidos elas têm ganhado destaque no diagnóstico diferencial de infecções no SNC. As atuais técnicas de imagem são sensíveis para detectar uma anormalidade, localizá-la, e em muitos casos categorizar a lesão como de origem infecciosa e/ou inflamatória, neoplásica ou vascular. Este ensaio ilustra os achados de ressonância magnética e tomografia computadorizada mais comuns nas infecções fúngicas do SNC baseadas na experiência do Serviço de Radiologia do Hospital de Clínicas de Porto Alegre.

The central vein sign in multiple sclerosis: a biomarker evaluated on a 3T MRI scanner

The central vein sign (CVS) is a promising MRI biomarker in multiple sclerosis (MS). CVS has recently been proposed to improve the accuracy and speed of MS diagnosis. Evidence indicates that the presence of CVS in individual lesions can accurately differentiate MS from other diseases that mimic this condition, such as hypertensive microangiopathy, atypical demyelination, and neuromyelitis optica. Most studies have used 7T MRI scanners, which limits their clinical applicability. Recently, it has been demonstrated that the fusion of the FLAIR and SWI sequences, generating FLAIR*, allows CVS visualization even on 3T scanners. Many studies have confirmed that CVS at 3T is a specific imaging finding for MS. (AU)

Topoisomerase II Is Crucial for Fork Convergence during Vertebrate Replication Termination.

Termination of DNA replication occurs when two replication forks converge upon the same stretch of DNA. Resolution of topological stress by topoisomerases is crucial for fork convergence in bacteria and viruses, but it is unclear whether similar mechanisms operate during vertebrate termination. Using Xenopus egg extracts, we show that topoisomerase II (Top2) resolves topological stress to prevent converging forks from stalling during termination. Under these conditions, stalling arises due to an inability to unwind the final stretch of DNA ahead of each fork. By promoting fork convergence, Top2 facilitates all downstream events of termination. Converging forks ultimately overcome stalling independently of Top2, indicating that additional mechanisms support fork convergence. Top2 acts throughout replication to prevent the accumulation of topological stress that would otherwise stall converging forks. Thus, termination poses evolutionarily conserved topological problems that can be mitigated by careful execution of the earlier stages of replication.

Serotonin Transporter Binding Potentials in Brain of Juvenile Monkeys 1 Year After Discontinuation of a 2-Year Treatment With Fluoxetine.

BACKGROUND: The potential long-term effects of childhood fluoxetine therapy on brain serotonin systems were studied using a nonhuman primate model, the rhesus monkey. METHODS: Juvenile male rhesus (1-4 years of age, corresponding to 4-11 years of age in children) were treated orally with fluoxetine (2 mg/kg) or vehicle daily for 2 years and removed from treatment during the third year. Each treatment group was assigned an equal number of subjects with low and high transcription polymorphisms of MAOA. One year after discontinuation of treatment, positron emission tomography scans were conducted (n = 8 treated monkeys, n = 8 control monkeys) using [11C]DASB to quantify serotonin transporter in 16 cortical and subcortical regions. RESULTS: Fluoxetine-treated monkeys with MAOA low transcription polymorphism had significantly lower [11C]DASB binding potentials than control monkeys. This finding was seen throughout the brain but was strongest in prefrontal and cingulate cortices. The MAOA × fluoxetine interaction was enhanced by binding potentials that were nonsignificantly higher in monkeys with high transcription polymorphism. CONCLUSIONS: Juvenile fluoxetine treatment has residual posttreatment effects on brain serotonin transporter that depend on MAOA genotype. MAOA genotype may be important to consider when treating children with fluoxetine.

La comunicación pedagógica en los escenarios de aprendizaje / Pedagogic communication in learning scenarios

La calidad de la educación y su impacto en el rol docente es de gran importancia, lo que conlleva a afirmar que no hay un sistema que no tenga interés por mejorar la educación y formación de los futuros profesionales, para ello debe contarse obligatoriamente con el profesorado. La actualidad es una época promisoria para el estudio de la comunicación y su impacto social. Toda comunicación que contribuya a perfeccionar la personalidad tiene un carácter pedagógico, de lo que se infiere su valor en la solución de los diferentes problemas humanos producidos dentro de las relaciones interpersonales en la sociedad contemporánea. Nuestro objetivo es valorar las características de la comunicación pedagógica en los escenarios de aprendizaje(AU)

The quality of education and its impact on the teaching role is of great importance, which leads to affirming that there is no system that does not feel deeply concerned about improving the education and training of future professionals, Therefore, the teaching staff must necessarily be relied upon. The present is a promising time for studying communication and its social impact. Any communication that contributes to perfecting the personality has a pedagogical character, from which its value is inferred in the solution of the different human problems produced within the interpersonal relationships in contemporary society. Our objective is to assess the characteristics of pedagogical communication in learning scenarios(AU)

La Universidad como institución pertinente en el avance de la sociedad / The University as an institution pertinent to the advance of the society

La sociedad y la Universidad tienen una relación directa, bilateral e indisoluble vinculada al desarrollo histórico, social, político, económico y cultural de las naciones. Ante la complejidad de los desafíos mundiales, presentes y futuros, la educación superior tiene el encargo social de hacer avanzar nuestra comprensión de problemas polifacéticos con dimensiones sociales, económicas, científicas y culturales, así como nuestra capacidad de hacerles frente. La Educación Superior debe asumir el liderazgo social en materia de creación de conocimientos para abordar con éxito los grandes retos mundiales, desafío de la emergente sociedad del conocimiento. El objetivo de este trabajo es valorar la correspondencia entre la Universidad y su vínculo con la sociedad. Además se pretende abordar consideraciones relacionadas con valores sociales y humanos de la educación superior(AU)

Society and the university have a direct, bilateral and indissoluble relationship associated to the historical, social, political, economic and cultural development of nations. Given the complexity of global, present and future challenges, higher education has the social responsibility to advance our understanding of multifaceted problems with social, economic, scientific and cultural dimensions, as well as our ability to cope with them. Higher education must assume the social leadership in the creation of knowledge to successfully tackle the great challenges worldwide, a challenge of the emerging society of knowledge. The purpose of this paper is to assess the correspondence between the university and its relationship with society. In addition, it is aimed at addressing considerations related to the social and human values of higher education(AU)