Carlos Gilberto Carlotti

Depression is a common neuropsychiatric sequela after aneurysmal subarachnoid hemorrhage (aSAH), yet its relationship to hemorrhage severity, aneurysm location, and functional outcome remains unclear. We examined associations of post-aSAH depression with Fisher grade, aneurysm location, and modified Rankin Scale (mRS) score in a single-center cohort. A retrospective observational study included 606 adult patients with aSAH. Only patients with documented outpatient follow-up assessing depression status were analyzed. Depression was defined as a clinical diagnosis documented during follow-up. A Fisher grade was assigned based on admission computed tomography (CT) imaging analysis. Functional outcomes were measured using the mRS. Group comparisons used chi-squared or Fisher's exact tests for categorical variables and Welch's t-tests for continuous variables. Ordinal logistic regression evaluated associations between Fisher grade, mRS, and depression. Depression was documented in 53 patients (8.7%). Age did not differ between groups (p = 0.654), and female sex showed a nonsignificant trend toward higher depression prevalence (Fisher's exact p = 0.078). Aneurysm circulation and anatomical location were not associated with depression (p = 0.409 and 0.151, respectively). Depression frequency increased with higher Fisher grades; ordinal modeling showed that each 1-grade increase was associated with higher odds of depression (OR: 1.21, 95% CI: 1.02–1.42; p = 0.027). Worse functional outcomes were strongly associated with depression, with each 1-point increase in mRS conferring higher odds (OR: 1.70, 95% CI: 1.39–2.08; p < 0.001). Post-aSAH depression was associated with hemorrhage severity and poorer functional outcomes but not with aneurysm location. These findings support structured depression surveillance in patients with higher Fisher grades and worse mRS scores.

Pilocytic astrocytoma (PA) is a rare, typically benign brain tumor classified as a low-grade glioma. Its occurrence during pregnancy is uncommon, but physiological changes in gestation—including hormonal shifts and altered immune and vascular dynamics—may influence tumor behavior, potentially leading to progression or symptom onset. The management of brain tumors in pregnant patients requires careful consideration of both maternal and fetal outcomes. We report the case of a 17-year-old pregnant patient at 27 weeks' gestation who presented with persistent vomiting and progressive neurological symptoms. The initial hypothesis was hyperemesis gravidarum, followed by subsequent identification of a posterior fossa mass. Brain magnetic resonance imaging (MRI) revealed a cerebellar tumor with obstructive hydrocephalus. Surgical resection via suboccipital craniectomy was performed with favorable maternal and fetal outcomes. Histopathology confirmed a diagnosis of pilocytic astrocytoma. A ventriculoperitoneal shunt was later placed for persistent hydrocephalus. The pregnancy progressed uneventfully, and the patient delivered a healthy infant at term. This case highlights the importance of early neuroimaging in pregnant patients with atypical or refractory symptoms, as well as the feasibility of neurosurgical intervention in the late second to early third trimester. A multidisciplinary approach is essential to optimize outcomes. Central nervous system (CNS) tumors should be considered in the differential diagnosis of persistent emesis and neurological complaints during pregnancy.

The University of São Paulo (USP), through its Environmental Policy and under the coordination of the Superintendence of Environmental Management (SGA), has been promoting sustainability initiatives across its campuses. One of the most recent efforts is the USP Sustainability Program (USPSusten), which supports teaching, research, outreach, and shared management activities focused on socio-environmental sustainability, carried out by faculty and postdoctoral researchers. Highlighted projects include: (a) the Bioenergy and Biofertilizer Production Plant (BBPP), which uses organic waste from campus dining halls and green areas at the main campus (CUASO) to produce biogas and fertilizers; (b) a pilot plant for fueling hydrogen-powered buses, with a range of 240 km; (c) photovoltaic energy generation, with the potential to meet up to 27% of contracted electricity demand; and (d) greenhouse gas inventories, based on the GHG Protocol methodology. The BBPP, in operation since May 2021, processes organic waste to generate an average of 2,800 kWh/month, with an average output of 136 kWh per ton of waste. The hydrogen fuel project uses ethanol as a renewable energy source and aims to reduce CO₂eq emissions per capita by up to 72% compared to conventional combustion vehicles. Solar generation has shown economic feasibility for units consuming over 100 MWh/month. The emission inventory, structured through an action-research approach, involves pilot units within USP and highlights the need for improvements in the use of refrigerant gases in buildings and anesthetic gases in hospitals. These integrated efforts demonstrate the University’s commitment to conserving natural resources and enhancing quality of life.

Gaucher disease (GD) is an autosomal recessive disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Although enzyme replacement therapy (ERT) remains the standard of care for non-neuropathic GD patients, its high cost significantly limits accessibility. To enhance production efficiency, we developed a lentiviral system encoding a codon-optimized GCase gene driven by the human elongation factor 1a (hEF1α) promoter for stable production in human cell lines. A functional lentiviral vector, LV_EF1α_GBA_Opt, was generated at a titer of 7.88 × 10⁸ LV particles/mL as determined by qPCR. Six transduction cycles were performed at a multiplicity of infection of 30–50. The transduced heterogeneous human cell population showed GCase-specific activity of 307.5 ± 53.49 nmol/mg protein/h, which represents a 3.21-fold increase compared to wild-type 293FT cells (95.58 ± 16.5 nmol/mg protein/h). Following single-cell cloning, two clones showed specific activity of 763.8 ± 135.1 and 752.0 ± 152.1 nmol/mg/h (clones 15 and 16, respectively). These results show that codon optimization, a lentiviral delivery system, and clonal selection together enable the establishment of stable human cell lines capable of producing high levels of biologically active, synthetic recombinant GCase in vitro. Further studies are warranted for the functional validation in GD patient-derived fibroblasts and animal models.

Gaucher disease (GD) is an autosomal recessive disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Although enzyme replacement therapy (ERT) remains the most effective treatment for GD patients, its high cost significantly limits accessibility. To enhance production efficiency, we developed a lentiviral system encoding a codon-optimized GCase gene driven by the human elongation factor 1a (hEF1) promoter for stable production in human cell lines. A functional lentiviral vector, LV_EF1_GBA_Opt, was generated at a titer of 7.88 x 108 LV particles/mL as determined by qPCR. Six transduction cycles were performed at a multiplicity of infection of 30-50. The transduced heterogeneous human cell population showed GCase-specific activity of 307.5 ± 53.49 nmol/ mg protein/ h, which was 3.21-fold increase compared to virgin 293FT cells (95.58 ± 16.5 nmol/ mg protein/ h). Following single-cell cloning, two clones showed specific activity of 763.8 ± 135.1 and 752.0 ± 152.1 nmol/mg/h (clones 15 and 16, respectively). These results show that codon optimization, a lentiviral delivery system, and clonal selection together enable the establishment of stable human cell lines capable of producing high levels of biologically active, synthetic recombinant GCase in vitro. Further studies are warranted for the functional validation in GD patient-derived fibroblasts and animal models.

We are reporting the case of JB, a 28-year-old male who presented to our hospital in 2009. The patient reported a progressive increase in a known mass that had been deforming their head since 2005. He had suffered from a first-time seizure four years later (in 2009). Neurological examination revealed a large tumor protruding in the parietal region, which was confirmed by CT. A subsequent MRI demonstrated a hyperostotic contrast-enhancing parasagittal tumor occluding the middle third of the superior sagittal sinus, with cortical veins joining the sinus adjacent to the tumor.The patient was taken to the OR for a craniotomy and a resection of the tumor with cranioplasty in the same setting. The tumor was exposed by using a straight incision on the scalp. A craniotomy was performed around the tumor by using multiple burr holes; now the bone could be separated from the dura and removed. The intradural tumor was exposed, and a cortical vein draining into the tumor could not be preserved. Some residual tumor was left close to the anterior part of the superior sagittal sinus. The dura was reconstructed with pericranium, and the bony defect was closed with titanium mesh. The patient woke up initially paraplegic, but 7 days later, he started with proximal movements in both legs. Unfortunately, he died suddenly in the second postoperative week, due to pulmonary embolism. The case is reviewed in this manuscript to analyze the contributing factors of the complications that were observed and to suggest management strategies to avoid them.

A pandemia causada pelo vírus SARS-COV-2 exigiu mudanças nos procedimentos e rotinas acadêmicas em geral. Em março de 2020, a Universidade de São Paulo (USP) decidiu substituir temporariamente as aulas presenciais por ensino remoto on-line usando plataformas digitais. Devido ao número considerável de docentes (aproximadamente 6.000) e pós-graduandos (aproximadamente 30.000) dos 267 Programas de Pós-Graduação, a USP teve que enfrentar o desafio de lidar com novas formas de aprendizagem, bem como novas formas de viabilizar defesas de teses e dissertações. Para avaliar as mudanças necessárias durante a pandemia, a Pró-Reitoria de Pós-Graduação da Universidade realizou uma pesquisa, por meio de formulários contendo perguntas, a fim de permitir à comunidade acadêmica a identificação das melhores e mais eficientes práticas utilizadas pelos docentes, bem como fragilidades que devem ser superadas. Este artigo apresenta e discute os resultados dessa avaliação, considerando 1.454 respostas sobre defesas e 2.656 respostas sobre cursos on-line. Os resultados mostraram que a maioria dos docentes e alunos aprovou os procedimentos adotados, mas foram necessárias algumas melhorias em relação às sessões de defesa remota e estratégias de aprendizagem. O artigo também apresenta algumas ações imediatas realizadas pela USP para superar os desafios apresentados durante as atividades remotas.

Pediatric high-grade glioma (pHGG) is one of the most aggressive brain tumors. Treatment includes surgery, radiotherapy, chemotherapy, or combination therapy in children older than 3–5 years of age. These devastating tumors are influenced by the hypoxic microenvironment that coordinatively increases the expression of carbonic anhydrases (CA9 and CA12) that are involved in pH regulation, metabolism, cell invasion, and resistance to therapy. The synthetic sulphonamide Indisulam is a potent inhibitor of CAs. The aim of this study was to evaluate the effects of Indisulam on CA9 and CA12 enzymes in pHGG cell lines. Our results indicated that, under hypoxia, the gene and protein expression of CA9 and CA12 are increased in pHGG cells. The functional effects of Indisulam on cell proliferation, clonogenic capacity, and apoptosis were measured in vitro. CA9 and CA12 gene and protein expression were analyzed by RT-PCR and western blot. The treatment with Indisulam significantly reduced cell proliferation (dose-time-dependent) and clonogenic capacity (p < 0.05) and potentiated the effect of apoptosis (p < 0.01). Indisulam promoted an imbalance in the anti-apoptotic BCL2 and pro-apoptotic BAX protein expression. Our results demonstrate that Indisulam contributes to apoptosis via imbalance of apoptotic proteins (BAX/BCL2) and suggests a potential to overcome chemotherapy resistance caused by the regulation these proteins.

Introduction: Glioblastoma is the most prevalent primary malignant neoplasm of the central nervous system. It has increased its incidence, while the overall survival remains over 14 months. Purpose: The purpose is to evaluate the expression of the genes EGFR, PTEN, MGMT, and IDH1/2, and microRNAs miR-181b, miR-145, miR-149, and miR-128a in adhered cells (AC) and neurospheres (NS) from cell lines (T98G and U343) submitted to temozolomide (TMZ) and ionizing radiation (IR). Methods: T98G and U343 were treated with TMZ, IR, and TMZ+IR. The analysis of gene expression and miRNAs was performed using real-time PCR. Results: This study demonstrated: a) an improvement in the expression of IDH1 after IR and TMZ + IR in the NS (T98G); b) an increase in the expression of MGMT in NS (T98G) in IR groups and TMZ + IR. The expression of miRNAs results as a) AC (U343) expressed more miR-181b after TMZ, IR, and TMZ + IR; and miR-128a improved after TMZ, IR, and TMZ + IR; b) NS (T98G) after TMZ + IR expressed: miR-181b; miR-149; miR-145 and miR-128a; c) NS (U343) after IR huge expressed miR-149 and miR-145. Conclusion: IR was an independent and determining radioresistance factor in NS. However, we observed no complementarity action of oncomiRs regulation.