Artigos e Materiais de Revistas Científicas - LIM/43

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https://observatorio.fm.usp.br/handle/OPI/3767

A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.

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Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In Vivo
(2022) KE, W.; CHANDLER, M.; CEDRONE, E.; SAITO, R. F.; RANGEL, M. C.; JUNQUEIRA, M. De Souza; WANG, J.; SHI, D.; TRUONG, N.; RICHARDSON, M.; ROLBAND, L. A.; DRéAU, D.; BEDOCS, P.; CHAMMAS, R.; DOKHOLYAN, N. V.; DOBROVOLSKAIA, M. A.; AFONIN, K. A.
The unbalanced coagulation of blood is a life-threatening event that requires accurate and timely treatment. We introduce a user-friendly biomolecular platform based on modular RNA-DNA anticoagulant fibers programmed for reversible extracellular communication with thrombin and subsequent control of anticoagulation via a ""kill-switch""mechanism that restores hemostasis. To demonstrate the potential of this reconfigurable technology, we designed and tested a set of anticoagulant fibers that carry different thrombin-binding aptamers. All fibers are immunoquiescent, as confirmed in freshly collected human peripheral blood mononuclear cells. To assess interindividual variability, the anticoagulation is confirmed in the blood of human donors from the U.S. and Brazil. The anticoagulant fibers reveal superior anticoagulant activity and prolonged renal clearance in vivo in comparison to free aptamers. Finally, we confirm the efficacy of the ""kill-switch""mechanism in vivo in murine and porcine models.
Expanding the phenotypic spectrum of CLCN2-related leucoencephalopathy and ataxia
(2023) NOBREGA, Paulo R.; PAIVA, Anderson R. B. de; SOUZA, Katiane S.; SOUZA, Jorge Luiz B. de; LIMA, Pedro Lucas G. S. B.; SILVA, Delson Jose da; PITOMBEIRA, Milena Sales; BORGES, Viviennee K.; DIAS, Daniel A.; BISPO, Luciana M.; SANTOS, Carolina F.; FREUA, Fernando; SILVA, Paulo Diego S.; ALVES, Isabela S.; PORTELLA, Leonardo B.; CUNHA, Paulina R.; SALOMAO, Rubens Paulo A.; PEDROSO, Jose Luiz; MIYAJIMA, Veridiana P.; MIYAJIMA, Fabio; CALI, Elisa; WADE, Charles; SUDARSANAM, Annapurna; O'DRISCOLL, Mary; HAYTON, Tom; BARSOTTINI, Orlando G. P.; KLEBE, Stephan; KOK, Fernando; LUCATO, Leandro Tavares; HOULDEN, Henry; DEPIENNE, Christel; LYNCH, David S.; BRAGA-NETO, Pedro
Mutations in CLCN2 are a rare cause of autosomal recessive leucoencephalopathy with ataxia and specific imaging abnormalities. Very few cases have been reported to date. Here, we describe the clinical and imaging phenotype of 12 additional CLCN2 patients and expand the known phenotypic spectrum of this disorder. Informed consent was obtained for all patients. Patients underwent either whole-exome sequencing or focused/panel-based sequencing to identify variants. Twelve patients with biallelic CLCN2 variants are described. This includes three novel likely pathogenic missense variants. All patients demonstrated typical MRI changes, including hyperintensity on T2-weighted images in the posterior limbs of the internal capsules, midbrain cerebral peduncles, middle cerebellar peduncles and cerebral white matter. Clinical features included a variable combination of ataxia, headache, spasticity, seizures and other symptoms with a broad range of age of onset. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy and reinforces the finding that, although the imaging appearance is uniform, the phenotypic expression of this disorder is highly heterogeneous. Our findings expand the phenotypic spectrum of CLCN2-related leucoencephalopathy by adding prominent seizures, severe spastic paraplegia and developmental delay. Nobrega et al. describe 12 additional CLCN2 leucoencephalopathy patients expanding the phenotypic spectrum by adding prominent seizures, severe spastic paraplegia and developmental delay. All patients demonstrated typical MRI changes. They found three novel missense variants. This report is now the largest case series of patients with CLCN2-related leucoencephalopathy. Graphical abstract
Cryoablation of Benign Thyroid Nodules: Preliminary Experience in 3 Cases
(2023) FREITAS, Ricardo Miguel Costa de; VANDERLEI, Felipe Augusto Brasileiro; ROSENFELD, Matheus Gerhard; BORGES, Alessandra de Pinho Pimenta; KOWALSKI, Luiz Paulo; CHAMMAS, Maria Cristina
Validation of automated image co-registration integrated into in-house software for voxel-based internal dosimetry on single-photon emission computed tomography images
(2023) LEITÃO, André Luiz Alberti; FONDA, Uysha de Souza; BUCHPIGUEL, Carlos Alberto; WILLEGAIGNON, José; SAPIENZA, Marcelo Tatit
Abstract Objective: To develop an automated co-registration system and test its performance, with and without a fiducial marker, on single-photon emission computed tomography (SPECT) images. Materials and Methods: Three SPECT/CT scans were acquired for each rotation of a Jaszczak phantom (to 0°, 5°, and 10° in relation to the bed axis), with and without a fiducial marker. Two rigid co-registration software packages-SPM12 and NMDose-coreg-were employed, and the percent root mean square error (%RMSE) was calculated in order to assess the quality of the co-registrations. Uniformity, contrast, and resolution were measured before and after co-registration. The NMDose-coreg software was employed to calculate the renal doses in 12 patients treated with 177Lu-DOTATATE, and we compared those with the values obtained with the Organ Level INternal Dose Assessment for EXponential Modeling (OLINDA/EXM) software. Results: The use of a fiducial marker had no significant effect on the quality of co-registration on SPECT images, as measured by %RMSE (p = 0.40). After co-registration, uniformity, contrast, and resolution did not differ between the images acquired with fiducial markers and those acquired without. Preliminary clinical application showed mean total processing times of 9 ± 3 min/patient for NMDose-coreg and 64 ± 10 min/patient for OLINDA/EXM, with a strong correlation between the two, despite the lower renal doses obtained with NMDose-coreg. Conclusion: The use of NMDose-coreg allows fast co-registration of SPECT images, with no loss of uniformity, contrast, or resolution. The use of a fiducial marker does not appear to increase the accuracy of co-registration on phantoms.
Membrane-derived particles shed by PSMA-positive cells function as pro-angiogenic stimuli in tumors
(2023) MACHADO, Camila M. L.; SKUBAL, Magdalena; HAEDICKE, Katja; SILVA, Fabio P.; STATER, Evan P.; SILVA, Thais L. A. de O.; COSTA, Erico T.; MASOTTI, Cibele; OTAKE, Andreia H.; ANDRADE, Luciana N. S.; JUNQUEIRA, Mara de S.; HSU, Hsiao-Ting; DAS, Sudeep; LARNEY, Benedict Mc; PRATT, Edwin C.; ROMIN, Yevgeniy; FAN, Ning; MANOVA-TODOROVA, Katia; POMPER, Martin; GRIMM, Jan
Cell membrane-derived particles (Mp) are rounded membrane-enclosed particles that are shed from tumor cells. Mp are formed from tumor membranes and are capable of tumor targeting and immunotherapeutic agents because they share membrane homology with parental cells; thus, they are under consideration as a drug de-livery vehicle. Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein with enzymatic functionality, is highly expressed in Mp and extracellular vesicles (EV) from prostate cancer (PCa) with poor clinical prognosis. Although PSMA expression was previously shown in EV and Mp isolated from cell lines and from the blood of patients with high-grade PCa, no pathophysiological effects have been linked to PCa-derived Mp. Here, we compared Mp from PSMA-expressing (PSMA-Mp) and PSMA-non-expressing (WT-Mp) cells side by side in vitro and in vivo. PSMA-Mp can transfer PSMA and new phenotypic characteristics to the tumor micro -environment. The consequence of PSMA transfer to cells and increased secretion of vascular endothelial growth factor-A (VEGF-A), pro-angiogenic and pro-lymphangiogenic mediators, with increased 4E binding protein 1 (4EBP-1) phosphorylation.
Letter to the Editor: The theoretical challenges of routinely using [¹⁸F]FDG PET/MRI combined with chest HRCT for early cancer detection in asymptomatic patients
(2023) DUARTE, Paulo Schiavom
Cortical thickness is related to working memory performance after non-invasive brain stimulation
(2023) RAZZA, L. B.; VANDERHASSELT, M. A.; LUETHI, M. S.; REPPLE, J.; BUSATTO, G.; BUCHPIGUEL, C. A.; BRUNONI, A. R.; SILVA, P. H. R. da
Non-invasive brain stimulation (NIBS) probing the dorsolateral prefrontal cortex (DLPFC) has been shown to have little effect on working memory. The variability of NIBS responses might be explained by inter-subject brain anatomical variability. We investigated whether baseline cortical brain thickness of regions of interest was associated with working memory performance after NIBS by performing a secondary analysis of previously published research. Structural magnetic resonance imaging data were analyzed from healthy subjects who received transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and placebo. Twenty-two participants were randomly assigned to receive all the interventions in a random order. The working memory task was conducted after the end of each NIBS session. Regions of interest were the bilateral DLPFC, medial prefrontal cortex, and posterior cingulate cortex. Overall, 66 NIBS sessions were performed. Findings revealed a negative significant association between cortical thickness of the bilateral dorsolateral prefrontal cortex and reaction time for both tDCS (left: P=0.045, right: P=0.037) and iTBS (left: P=0.007, right: P=0.007) compared to placebo. A significant positive association was found for iTBS and posterior cingulate cortex (P=0.03). No association was found for accuracy. Our findings provide the first evidence that individual cortical thickness of healthy subjects might be associated with working memory performance following different NIBS interventions. Therefore, cortical thickness could explain -to some extent -the heterogeneous effects of NIBS probing the DLPFC.
Patentometric analysis as a subsid to the management of technological innovation: a case study in radiopharmaceuticals for cancer
(2023) CHAVES, Henrique Koch; SILVA, Julia Maria Brandao da; SILVEIRA, Carla Cristina de Freitas da; MARQUES, Fabio Luiz Navarro; MAGALHAES, Jorge Lima de
Objective: Prospect the evolution of patent applications onIdentify, extract, process data, organize and make available technological information in the form of graphical interfaces described in oncology patents containing the radioisotopes gallium-68 (68Ga), copper-64 (64Cu) and zirconium-89 (89Z) in order to understand the development of science and technology in the area.Method: The ORBIT Intelligence® platform from the company QUESTEL® was used to identify, extract, process the data, organize and make available the technological information in the form of graphical interfaces, analysis of the filed patents in force in the last 20 years in the main patent offices in the world.Result: For gallium-68, copper-64 and zirconium-89, respectively, 36, 18 and 10 families of patents containing the search terms described in the methodology were identified. In both cases, China stands out in the number of filed patent applications, depositing 61% of the total analyzed. It was also observed that many of the analyzed documents were deposited by universities, reinforcing the concept of company-university partnership. The results obtained point out that the area of this study continues to grow and the understanding of the information present in the patent documents makes itpossible to reflect on spaces to intensify the development of innovations in the oncology area.Conclusions: The results obtained demonstrate the relevance of information for the management of a country's technological development, which can serve as an efficient method to analyze, compare and monitor research and development activities in cancer and also support the planning processes organizations, as well as supporting public and private health policies.
Repeatability of brown adipose tissue activation measured by [¹⁸F]FDG PET after beta3-adrenergic stimuli in a mouse model
(2023) FARIA, Daniele de Paula; VERA, Cleinando Clemente da Silva; MARQUES, Fabio Luiz Navarro; SAPIENZA, Marcelo Tatit
This study aimed to evaluate the repeatability of brown adipose tissue (BAT) activation measured by [F-18]FDG-PET after beta3-adrenergic stimuli with CL316243 in mice.Methods: Male C57BL/6 mice underwent [F-18]FDG-PET at baseline without stimulation (T0-NS), on three consecutive days after intravenous administration of the selective beta 3-adrenergic agonist CL316243 (T1-CL, T2-CL, T3-CL), and without stimuli after 1 and 2 weeks (T7-NS and T14-NS). The standardized uptake value (SUVmax), BAT metabolic volume (BMV), and total BAT glycolysis (TBG) were measured in each scanning session, with statistical groupwise comparisons by ANOVA and post hoc Tukey test.Results: SUVmax, BMV, and TBG values showed no significant differences between the three PET scans without stimuli, but were significantly higher after CL316243 administration (p < 0.0001). The mean coefficient of variation (CoV) of PET within individuals was 49 % at baseline but only 9 % with pharmacological stimulation.Conclusions: The study demonstrated that administration of the selective beta 3-adrenergic receptor agonist CL316243 (CL) in mice leads to consistent metabolic activation of brown adipose tissue (BAT), as measured by [F-18]FDG-PET. We also demonstrated metabolic activation by repeated pharmacological challenge, without evidence of hysteresis. Thus, the methods used in the current work should serve for further studies on BAT metabolism in experimental animals, with translational value for clinical research.
Development and external validation of a multivariable [⁶⁸Ga]Ga-PSMA-11 PET-based prediction model for lymph node involvement in men with intermediate or high-risk prostate cancer
(2023) MUEHLEMATTER, Urs J.; SCHWEIGER, Lilit; FERRARO, Daniela A.; HERMANNS, Thomas; MAURER, Tobias; HECK, Matthias M.; RUPP, Niels J.; EIBER, Matthias; RAUSCHER, Isabel; BURGER, Irene A.
PurposeTo develop and evaluate a lymph node invasion (LNI) prediction model for men staged with [Ga-68]Ga-PSMA-11 PET.MethodsA consecutive sample of intermediate to high-risk prostate cancer (PCa) patients undergoing [Ga-68]Ga-PSMA-11 PET, extended pelvic lymph node dissection (ePLND), and radical prostatectomy (RP) at two tertiary referral centers were retrospectively identified. The training cohort comprised 173 patients (treated between 2013 and 2017), the validation cohort 90 patients (treated between 2016 and 2019). Three models for LNI prediction were developed and evaluated using cross-validation. Optimal risk-threshold was determined during model development. The best performing model was evaluated and compared to available conventional and multiparametric magnetic resonance imaging (mpMRI)-based prediction models using area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA).ResultsA combined model including prostate-specific antigen, biopsy Gleason grade group, [Ga-68]Ga Ga-PSMA-11 positive volume of the primary tumor, and the assessment of the [Ga-68]Ga-PSMA-11 report N-status yielded an AUC of 0.923 (95% CI 0.863-0.984) in the external validation. Using a cutoff of >= 17%, 44 (50%) ePLNDs would be spared and LNI missed in one patient (4.8%). Compared to conventional and MRI-based models, the proposed model showed similar calibration, higher AUC (0.923 (95% CI 0.863-0.984) vs. 0.700 (95% CI 0.548-0.852)-0.824 (95% CI 0.710-0.938)) and higher net benefit at DCA.ConclusionsOur results indicate that information from [Ga-68]Ga-PSMA-11 may improve LNI prediction in intermediate to high-risk PCa patients undergoing primary staging especially when combined with clinical parameters. For better LNI prediction, future research should investigate the combination of information from both PSMA PET and mpMRI for LNI prediction in PCa patients before RP.
Comparison of Oral and IV ¹⁸F-NaF PET/CT Administration in the Assessment of Bone Metastases in Patients With Breast or Prostate Cancers
(2023) ROCHA, Nelisa Helena; ZACCHI, Samara Riguete; SADO, Heitor Naoki; BUCHPIGUEL, Carlos Alberto; DUARTE, Paulo Schiavom; SAPIENZA, Marcelo Tatit
PurposeThe aim of this study was to compare oral and IV administrations of F-18-NaF PET/CT for detection of suspicious bone metastatic lesions of breast and prostate cancers.Patients and MethodsThirty-six patients with breast (n = 23) or prostate (n = 13) cancers and high risk for bone metastases were prospectively evaluated. All patients underwent 2 PET/CT studies after IV and oral F-18-NaF administration within a 2 to 23 days interval between them. The maximum SUVs from the same suspicious lesions (& LE;5 index lesions per patient) in both studies were measured. The target-to-background ratio (TBR), defined as the relation between the lesion maximum SUV and the whole skeletal mean SUV, was calculated for each lesion. The TBRs in the same lesion calculated using the 2 administration routes were compared. The agreements between 2 physicians in the definition of the number of lesions in both studies were also assessed using weighted & kappa;.ResultsOne hundred thirty-four pairs of lesions were analyzed. There was no significant statistical difference between the median TBRs (P = 0.212) for IV (10.33) and oral (10.85). Excellent intraobserver agreement was observed between IV and oral routes: weighted & kappa; of 1.0 (95% confidence interval, 0.92-1.0) and 0.92 (95% confidence interval, 0.81-0.99) for physicians 1 and 2, respectively. The interobserver coefficients were 0.82 and 0.87 for ""oral versus oral"" and ""IV versus IV,"" respectively.Conclusions(18)F-NaF PET/CT studies using oral and IV routes present comparable performance; thus, it is possible to use oral route in patients with difficult venous access.
A Prospective Cross-Sectional Study on the Performance of the 2021 CKD-EPI Equations Without Race in a Multiracial Population of Adults With Solid Tumors in Brazil
(2023) SILVA, Veronica T. Costa e; JR, Luiz A. Gil; INKER, Lesley A.; CAIRES, Renato A.; COSTALONGA, Elerson; COURA-FILHO, George; SAPIENZA, Marcelo T.; JR, Gilberto Castro; ESTEVEZ-DIZ, Maria D. P.; ZANETTA, Dirce Maria T.; ANTONANGELO, Leila; MARCAL, Lia; TIGHIOUART, Hocine; MIAO, Shiyuan; MATHEW, Paul; LEVEY, Andrew S.; BURDMANN, Emmanuel A.
External validation of a machine learning based algorithm to differentiate hepatic mucinous cystic neoplasms from benign hepatic cysts
(2023) FURTADO, Felipe S. S.; BADENES-ROMERO, Alvaro; HESAMI, Mina; MOSTAFAVI, Leila; NAJMI, Zahra; QUEIROZ, Marcelo; MOJTAHED, Amirkasra; ANDERSON, Mark A. A.; CATALANO, Onofrio A. A.
Purpose To externally validate an algorithm for non-invasive differentiation of hepatic mucinous cystic neoplasms (MCN) from benign hepatic cysts (BHC), which differ in management. Methods Patients with cystic liver lesions pathologically confirmed as MCN or BHC between January 2005 and March 2022 from multiple institutions were retrospectively included. Five readers (2 radiologists, 3 non-radiologist physicians) independently reviewed contrast-enhanced CT or MRI examinations before tissue sampling and applied the 3-feature classification algorithm described by Hardie et al. to differentiate between MCN and BHC, which had a reported accuracy of 93.5%. The classification was then compared to the pathology results. Interreader agreement between readers across different levels of experience was evaluated with Fleiss' Kappa. Results The final cohort included 159 patients, median age of 62 years (IQR [52.0, 70.0]), 66.7% female (106). Of all patients, 89.3% (142) had BHC, and the remaining 10.7% (17) had MCN on pathology. Agreement for class designation between the radiologists was almost perfect (Fleiss' Kappa 0.840, p < 0.001). The algorithm had an accuracy of 98.1% (95% CI [94.6%, 99.6%]), a positive predictive value of 100.0% (95% CI [76.8%, 100.0%]), a negative predictive value of 97.9% (95% CI [94.1%, 99.6%]), and an area under the receiver operator characteristic curve (AUC) of 0.911 (95% CI [0.818, 1.000]). Conclusion The evaluated algorithm showed similarly high diagnostic accuracy in our external, multi-institutional validation cohort. This 3-feature algorithm is easily and rapidly applied and its features are reproducible among radiologists, showing promise as a clinical decision support tool. [GRAPHICS] .
Photobiomodulation Therapy Mitigates Salivary Gland Damage Induced by Radioactive Iodine Ablation
(2023) CAMPOS, Luana; MAGLIANO, Gabriela Campos; HOTSUMI, Andressa Matucci; FARIA, Daniele de Paula; GARCEZ, Alexandre Teles; GODOY, Fernando; ARANA-CHAVEZ, Victor Elias; SIMOES, Alyne
(1) Background: Thyroid tissue ablation with radioactive iodine (RAI) has been successfully used in the treatment of differentiated thyroid cancers. However, as a side effect, RAI may induce salivary gland (SG) hypofunction, which has been alternatively managed with photobiomodulation therapy (PBMT). In our study, we assessed the effects of RAI on the SGs and further analyzed whether PBMT can minimize tissue damage. (2) Methods: Balb/c mice were allocated into three groups, as follows: RI, submitted to RAI orally; RIL, similar to RI, but with PBMT for SG hypofunction; and C, control group. The animals were euthanized on days 0, 10, and 90 after RAI. (3) Results: A decrease in tri-iodothyronine (T3) and thyroxine (T4) serum levels was observed both in the RI and RIL groups. In addition, a decrease in SG weight and morphological alterations were shown in the RI group throughout the experimental period, as well as a significant increase in total protein and peroxidase concentrations, and catalase activity. On day 90, the RI group presented less collagen and fewer sodium/iodine channels, with higher rates of cell apoptosis. Pertechnetate ((NaTcO4)-Tc-99m) uptake was also affected in the RI group in all experimental times. Interestingly, although the RIL group also presented some alterations regarding these parameters, they were not statistically different from those of the C group on day 90. (4) Conclusions: Our results provide evidence that RAI induces harmful effects on the SGs, which can be successfully managed with PBMT.
Ultrasound in cervical traumatic neuromas after neck dissection in thyroid carcinoma patients: descriptive analysis and diagnostic accuracy
(2023) MARCOS, Vinicius Neves; DANILOVIC, Debora Lucia Seguro; PEREIRA, Fernando Linhares; TSUNEMI, Miriam Harumi; KULCSAR, Marco Aurelio Vamondes; HOFF, Ana Oliveira; DOMINGUES, Regina Barros; CHAMMAS, Maria Cristina; FREITAS, Ricardo Miguel Costa de
Objective: Cervical traumatic neuromas (CTNs) may appear after lateral neck dissection for metastatic thyroid carcinoma. If they are misdiagnosed as metastatic lymph nodes (LNs) in follow-up neck ultrasound (US), unnecessary and uncomfortable fine-needle aspiration biopsy are indicated. The present study aimed to describe US features of CTNs and to assess the US performance in distinguishing CTNs from abnormal LNs. Subjects and methods: Retrospective evaluation of neck US images of 206 consecutive patients who had lateral neck dissection as a part of thyroid cancer treatment to assess CTN's US features. Diagnostic accuracy study to evaluate US performance in distinguishing CTNs from abnormal LNs was performed. Results: Eight-six lateral neck nodules were selected for analysis: 38 CTNs and 48 abnormal LNs. CTNs with diagnostic cytology were predominantly hypoechogenic (100% vs. 45%; P = 0.008) and had shorter diameters than inconclusive cytology CTNs: short axis (0.39 cm vs. 0.50 cm; P = 0.03) and long axis (1.64 cm vs. 2.35 cm; P = 0.021). The US features with the best accuracy to distinguish CTNs from abnormal LNs were continuity with a nervous structure, hypoechogenic internal lines, short/long axis ratio = 0.42, absent Doppler vascularization, fusiform morphology, and short axis = 0.48 cm. Conclusion: US is a very useful method for assessing CTNs, with good performance in distinguishing CTNs from abnormal LNs.
Transcriptomic analysis reveals distinct adaptive molecular mechanism in the hippocampal CA3 from rats susceptible or not-susceptible to hyperthermia-induced seizures
(2023) BANDO, Silvia Y.; BERTONHA, Fernanda B.; MENEZES, Pedro H. N.; TAKAHARA, Andre K.; KHALED, Nathalia A.; SANTOS, Paula; JUNQUEIRA, Mara S.; CESAR, Roberto M.; MOREIRA-FILHO, Carlos A.
Febrile seizures during early childhood are a relevant risk factor for the development of mesial temporal lobe epilepsy. Nevertheless, the molecular mechanism induced by febrile seizures that render the brain susceptible or not-susceptible to epileptogenesis remain poorly understood. Because the temporal investigation of such mechanisms in human patients is impossible, rat models of hyperthermia-induced febrile seizures have been used for that purpose. Here we conducted a temporal analysis of the transcriptomic and microRNA changes in the ventral CA3 of rats that develop (HS group) or not-develop (HNS group) seizures after hyperthermic insult on the eleventh postnatal day. The selected time intervals corresponded to acute, latent, and chronic phases of the disease. We found that the transcriptional differences between the HS and the HNS groups are related to inflammatory pathways, immune response, neurogenesis, and dendritogenesis in the latent and chronic phases. Additionally, the HNS group expressed a greater number of miRNAs (some abundantly expressed) as compared to the HS group. These results indicate that HNS rats were able to modulate their inflammatory response after insult, thus presenting better tissue repair and re-adaptation. Potential therapeutic targets, including genes, miRNAs and signaling pathways involved in epileptogenesis were identified.
Brain glucose metabolism and gray matter volume in retired professional soccer players: a cross-sectional [F-18]FDG-PET/MRI study
(2023) ARANHA, Mateus Rozalem; COUTINHO, Artur Martins; CARNEIRO, Camila de Godoi; PASTORELLO, Bruno Fraccini; STUDART-NETO, Adalberto; GUARIGLIA, Carla Cristina; TSUNEMI, Miriam Harumi; MOREIRA, Everton Luis Santos; IANOF, Jessica Natuline; ANGHINAH, Renato; NITRINI, Ricardo; CERRI, Giovanni Guido; FORTEA, Juan; BUCHPIGUEL, Carlos Alberto; LEITE, Claudia Costa
Background Professional soccer athletes are exposed to repetitive head impacts and are at risk of developing chronic traumatic encephalopathy. Objective To evaluate regional brain glucose metabolism (rBGM) and gray matter (GM) volume in retired soccer players (RSPs). Methods Male RSPs and age and sex-matched controls prospectively enrolled between 2017 and 2019 underwent neurological and neuropsychological evaluations, brain MRI and [F-18]FDG-PET in a 3.0-Tesla PET/MRI scanner. Visual analysis was performed by a blinded neuroradiologist and a blinded nuclear physician. Regional brain glucose metabolism and GM volume were assessed using SPM8 software. Groups were compared using appropriate statistical tests available at SPM8 and R. Results Nineteen RSPs (median [IQR]: 62 [50-64.5] years old) and 20 controls (60 [48-73] years old) were included. Retired soccer players performed worse on mini-mental state examination, digit span, clock drawing, phonemic and semantic verbal fluency tests, and had reduced rBGM in the left temporal pole (pFDR = 0.008) and the anterior left middle temporal gyrus (pFDR = 0.043). Semantic verbal fluency correlated with rBGM in the right hippocampus, left temporal pole, and posterior left middle temporal gyrus (p <= 0.042). Gray matter volume reduction was observed in similar anatomic regions but was less extensive and did not survive correction for multiple comparisons (pFDR >= 0.085). Individual [18F]FDG-PET visual analysis revealed seven RSPs with overt hypometabolism in the medial and lateral temporal lobes, frontal lobes, and temporoparietal regions. Retired soccer players had a higher prevalence of septum pellucidum abnormalities on MRI. Conclusion Retired soccer players had reduced rBGM and GM volume in the temporal lobes and septum pellucidum abnormalities, findings possibly related to repetitive head impacts.
Influence on voxel-based dosimetry: noise effect on absorbed dose dosimetry at single time-point versus sequential single-photon emission computed tomography
(2023) FONDA, Uysha de S.; LEITAO, Andre L. A.; PAIVA, Marcia M. D. P.; WILLEGAIGNON, Jose; JOSEFSSON, Anders; BUCHPIGUEL, Carlos A.; SAPIENZA, Marcelo T.
ObjectiveThe purpose of this study was to evaluate how statistical fluctuation in single-photon emission computed tomography (SPECT) images propagate to absorbed dose maps. MethodsSPECT/computed tomography (CT) images of iodine-131 filled phantoms, using different acquisition and processing protocols, were evaluated using STRATOS software to assess the absorbed dose distribution at the voxel level. Absorbed dose values and coefficient of variation (COV) were analyzed for dosimetry based on single time-point SPECT images and time-integrated activities of SPECT sequences with low and high counts. ResultsConsidering dosimetry based on a single time-point, the mean absorbed dose was not significantly affected by total counts or reconstruction parameters, but the uniformity of the absorbed dose maps had an almost linear correlation with SPECT noise. When high- and low-count SPECT sequences were used to generate an absorbed dose map, the absorbed dose COV for each of the temporal sequences was slightly lower than the absorbed dose COV based on the single SPECT image with the highest count included in the sequence. ConclusionThe impact of changes in SPECT counts and reconstruction parameters is almost linear when dosimetry is based on isolated SPECT images, but less pronounced when dosimetry is based on sequential SPECTs.
[18F]FDG and [11C]PK11195 PET imaging in the evaluation of brown adipose tissue-effects of cold and pharmacological stimuli and their association with crotamine intake in a male mouse model
(2023) FARIA, Daniele de Paula; CAMPEIRO, Joana D'Arc; JUNQUEIRA, Mara de Souza; REAL, Caroline Cristiano; MARQUES, Fabio Luiz Navarro; HAYASHI, Mirian Akemi Furuie; SAPIENZA, Marcelo Tatit
This study aimed to evaluate the role of positron emission tomography (PET) with [11C]PK11195 and [18F]FDG in the characterization of brown adipose tissue (BAT). Methods: Male C57BL/6 mice were studied with the glucose analogue [18F]FDG (n = 21) and the TSPO mitochondrial tracer [11C]PK11195 (n = 28), without stimulus and after cold (6-9 degrees C) or beta-agonist (CL316243) stimuli. PET studies were performed at baseline and after 21 days of daily treatment with crotamine, which is a peptide described to induce adipocyte tissue browning and to increase BAT metabolism. Tracer uptake (SUVmax) was measured in the interscapular BAT and translocator protein 18 kDa (TSPO) expression was evaluated by immunohistochemistry. Results: The cold stimulus increased [18F]FDG uptake compared to no-stimulus (5.21 & PLUSMN; 1.05 vs. 2.03 & PLUSMN; 0.21, p < 0.0001) and to beta-agonist stimulus (2.65 & PLUSMN; 0.39, p = 0.0003). After 21 days of treatment with crotamine, there was no significant difference in the [18F]FDG uptake compared to the baseline in the no-stimulus group and in the cold-stimulus group, with a significant increase in uptake after CL stimulus (baseline: 2.65 & PLUSMN; 0.39; 21 days crotamine: 4.77 & PLUSMN; 0.81, p = 0.0003). Evaluation of [11C]PK11195 at baseline shows that CL stimulus increases the BAT uptake compared to no-stimulus (4.47 & PLUSMN; 0.66 vs. 3.36 & PLUSMN; 0.68, p = 0.014). After 21 days of treatment with crotamine, there was no significant difference in the [11C]PK11195 uptake compared to the baseline in the no-stimulus group (2.94 & PLUSMN; 0.58, p = 0.7864) and also after CL stimulus (3.55 & PLUSMN; 0.79, p = 0.085). TSPO expression correlated with [11C]PK11195 uptake (r = 0.83, p = 0.018) but not with [18F]FDG uptake (r = 0.40, p = 0.516). Conclusions: [11C]PK11195 allowed the identification of BAT under thermoneutral conditions or after beta3adrenergic stimulation in a direct correlation with TSPO expression. The beta-adrenergic stimulus, despite presenting a lower intensity of glycolytic activation compared to cold at baseline, allowed the observation of an increase in BAT uptake of [18F]FDG after 21 days of crotamine administration. Although some limitations were observed for the metabolic changes induced by crotamine, this study reinforced the potential of using [11C] PK11195 and/or [18F]FDG-PET to monitor the activation of BAT.
Bioluminescence Imaging and ICP-MS Associated with SPION as a Tool for Hematopoietic Stem and Progenitor Cells Homing and Engraftment Evaluation
(2023) GARRIGOS, Murilo M.; OLIVEIRA, Fernando A.; NUCCI, Mariana P.; MAMANI, Javier B.; DIAS, Olivia F. M.; REGO, Gabriel N. A.; JUNQUEIRA, Mara S.; COSTA, Cicero J. S.; SILVA, Lucas R. R.; ALVES, Arielly H.; VALLE, Nicole M. E.; MARTI, Luciana; GAMARRA, Lionel F.
Bone marrow transplantation is a treatment for a variety of hematological and non-hematological diseases. For the transplant success, it is mandatory to have a thriving engraftment of transplanted cells, which directly depends on their homing. The present study proposes an alternative method to evaluate the homing and engraftment of hematopoietic stem cells using bioluminescence imaging and inductively coupled plasma mass spectrometry (ICP-MS) associated with superparamagnetic iron oxide nanoparticles. We have identified an enriched population of hematopoietic stem cells in the bone marrow following the administration of Fluorouracil (5-FU). Lately, the cell labeling with nanoparticles displayed the greatest internalization status when treated with 30 mu g Fe/mL. The quantification by ICP-MS evaluate the stem cells homing by identifying 3.95 +/- 0.37 mu g Fe/mL in the control and 6.61 +/- 0.84 mu g Fe/mL in the bone marrow of transplanted animals. In addition, 2.14 +/- 0.66 mg Fe/g in the spleen of the control group and 2.17 +/- 0.59 mg Fe/g in the spleen of the experimental group was also measured. Moreover, the bioluminescence imaging provided the follow up on the hematopoietic stem cells behavior by monitoring their distribution by the bioluminescence signal. Lastly, the blood count enabled the monitoring of animal hematopoietic reconstitution and ensured the transplantation effectiveness.

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