WILSON JACOB FILHO

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Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/66, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • article 2 Citação(ões) na Scopus
    The influence of age and sex on the absolute cell numbers of the human brain cerebral cortex
    (2023) CASTRO-FONSECA, Emily; MORAIS, Viviane; SILVA, Camila G. da; WOLLNER, Juliana; FREITAS, Jaqueline; MELLO-NETO, Arthur F.; OLIVEIRA, Luiz E.; OLIVEIRA, Vilson C. de; LEITE, Renata E. P.; ALHO, Ana T.; RODRIGUEZ, Roberta D.; FERRETTI-REBUSTINI, Renata E. L.; SUEMOTO, Claudia K.; JACOB-FILHO, Wilson; NITRINI, Ricardo; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; TOVAR-MOLL, Fernanda; LENT, Roberto
    The human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in women's frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has similar to 10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity.
  • article 1 Citação(ões) na Scopus
    Crash Risk Predictors in Older Drivers: A Cross-Sectional Study Based on a Driving Simulator and Machine Learning Algorithms
    (2023) SILVA, V. C.; DIAS, A. S.; GREVE, J. M. D.; DAVIS, C. L.; SOARES, A. L. D. S.; BRECH, G. C.; AYAMA, S.; JACOB-FILHO, W.; BUSSE, A. L.; BIASE, M. E. M. de; CANONICA, A. C.; ALONSO, A. C.
    The ability to drive depends on the motor, visual, and cognitive functions, which are necessary to integrate information and respond appropriately to different situations that occur in traffic. The study aimed to evaluate older drivers in a driving simulator and identify motor, cognitive and visual variables that interfere with safe driving through a cluster analysis, and identify the main predictors of traffic crashes. We analyzed the data of older drivers (n = 100, mean age of 72.5 ± 5.7 years) recruited in a hospital in São Paulo, Brazil. The assessments were divided into three domains: motor, visual, and cognitive. The K-Means algorithm was used to identify clusters of individuals with similar characteristics that may be associated with the risk of a traffic crash. The Random Forest algorithm was used to predict road crash in older drivers and identify the predictors (main risk factors) related to the outcome (number of crashes). The analysis identified two clusters, one with 59 participants and another with 41 drivers. There were no differences in the mean of crashes (1.7 vs. 1.8) and infractions (2.6 vs. 2.0) by cluster. However, the drivers allocated in Cluster 1, when compared to Cluster 2, had higher age, driving time, and braking time (p < 0.05). The random forest performed well (r = 0.98, R2 = 0.81) in predicting road crash. Advanced age and the functional reach test were the factors representing the highest risk of road crash. There were no differences in the number of crashes and infractions per cluster. However, the Random Forest model performed well in predicting the number of crashes.
  • article 16 Citação(ões) na Scopus
    Neuropathological correlates of neuropsychiatric symptoms in dementia
    (2023) GIBSON, Lucy L.; GRINBERG, Lea T.; FFYTCHE, Dominic; LEITE, Renata E. P.; RODRIGUEZ, Roberta D.; FERRETTI-REBUSTINI, Renata E. L.; PASQUALUCCI, Carlos A.; NITRINI, Ricardo; JACOB-FILHO, Wilson; AARSLAND, Dag; SUEMOTO, Claudia K.
    Introduction Neuropsychiatric symptoms (NPS) are common in Lewy body disease (LBD), but their etiology is poorly understood. Methods In a population-based post mortem study neuropathological data was collected for Lewy body (LB) neuropathology, neurofibrillary tangles (NFT), amyloid beta burden, TDP-43, lacunar infarcts, cerebral amyloid angiopathy (CAA), and hyaline atherosclerosis. Post mortem interviews collected systematic information regarding NPS and cognitive status. A total of 1038 cases were included: no pathology (NP; n = 761), Alzheimer's disease (AD; n = 189), LBD (n = 60), and AD+LBD (n = 28). Results Hallucinations were associated with higher LB Braak stages, while higher NFT Braak staging was associated with depression, agitation, and greater number of symptoms in the Neuropsychiatric Inventory. Cases with dual AD+LBD pathology had the highest risk of hallucinations, agitation, apathy, and total symptoms but a multiplicative interaction between these pathologies was not significant. Discussion LB and AD pathology contribute differentially to NPS likely with an additive process contributing to the increased burden of NPS.
  • article 3 Citação(ões) na Scopus
    Transforming the invisible into the visible: disparities in the access to health in LGBT plus older people
    (2023) CRENITTE, Milton Roberto Furst; MELO, Leonardo Rabelo de; JACOB-FILHO, Wilson; AVELINO-SILVA, Thiago Junqueira
    Objectives: To compare variables of access to healthcare between the LGBT+ population aged 50 and over and those non-LGBT+.Methods: A cross-sectional study was carried out in Brazil through a confidential online questionnaire. The use of the health system was characterized by the number of preventive tests performed and measured by the PCATool-Brasil scale (a 10-point scale in which higher scores were associated with better assistance in healthcare). The association between being LGBT+ and access to health was analyzed in Poisson regression models.Results: 6693 participants (1332 LGBT+ and 5361 non-LGBT+) with a median age of 60 years were included. In the univariate analysis, it was observed not only lower scores on the PCATool scale (5.13 against 5.82, p < 0.001), but a greater proportion of individuals among those classified with the worst quintile of access to healthcare (< 4 points), 31% against 18% (p < 0.001). Being LGBT+ was an independent factor associated with worse access to health (PR = 2.5, 95% CI 2.04-3.06). The rate of screening cancer, for breast, colon, and cervical cancer was also found to be lower in the LGBT+ population. Conclusion: Healthcare access and health service experiences were worse in the LGBT+ group than in their non-LGBT peers. Inclusive and effective healthcare public policies are essential to promote healthy aging for all.
  • article 1 Citação(ões) na Scopus
    High Prevalence of Energy and Nutrients Inadequacy among Brazilian Older Adults
    (2023) MAGALHAES, Natalia Vieira; WAITZBERG, Dan Linetzky; LOPES, Natalia Correia; VICEDOMINI, Ana Carolina Costa; PRUDENCIO, Ana Paula Aguiar; JACOB-FILHO, Wilson; BUSSE, Alexandre Leopold; FERDINANDO, Douglas; ALVES, Tatiana Pereira; PEREIRA, Rosa Maria Rodrigues; TORRINHAS, Raquel Susana; BELARMINO, Giliane
    Poor nutrition increases the risk of diseases and adverse health outcomes in older adults. We evaluated the potential inadequacy of nutrient intake among older adults in Brazil and its association with body anthropometry and composition outcomes. Dietary intake was obtained from 295 community-living older adults (>60 years old), of both genders, using a seven-day food record. Nutrient inadequacy was further identified based on the Dietary Reference Intakes and European Guidelines. Skeletal muscle mass (SM), strength and performance, and the diagnosis of sarcopenia were assessed using reference methods. Nutritional inadequacy was high, with energy, dietary fiber, and six micronutrients exhibiting the greatest inadequacy levels (>80%). Energy intake was correlated with SM strength (p = 0.000) and performance (p = 0.001). Inadequate energy, fiber, and protein intakes influenced BMI, while inadequate intake of vitamin B6 directly affected the diagnosis of sarcopenia (p & LE; 0.005). Further research is required to investigate whether these inadequacies can be associated with other clinical health outcomes.
  • article 2 Citação(ões) na Scopus
    Postmortem Brains from Subjects with Diabetes Mellitus Display Reduced GLUT4 Expression and Soma Area in Hippocampal Neurons: Potential Involvement of Inflammation
    (2023) YONAMINE, Caio Yogi; PASSARELLI, Marisa; SUEMOTO, Claudia Kimie; PASQUALUCCI, Carlos Augusto; JACOB-FILHO, Wilson; ALVES, Venancio Avancini Ferreira; MARIE, Suely Kazue Nagahashi; CORREA-GIANNELLA, Maria Lucia; BRITTO, Luiz Roberto; MACHADO, Ubiratan Fabres
    Diabetes mellitus (DM) is an important risk factor for dementia, which is a common neurodegenerative disorder. DM is known to activate inflammation, oxidative stress, and advanced glycation end products (AGEs) generation, all capable of inducing neuronal dysfunctions, thus participating in the neurodegeneration progress. In that process, disturbed neuronal glucose supply plays a key role, which in hippocampal neurons is controlled by the insulin-sensitive glucose transporter type 4 (GLUT4). We investigated the expression of GLUT4, nuclear factor NF-kappa B subunit p65 [NFKB (p65)], carboxymethyllysine and synapsin1 (immunohistochemistry), and soma area in human postmortem hippocampal samples from control, obese, and obese+DM subjects (41 subjects). Moreover, in human SH-SY5Y neurons, tumor necrosis factor (TNF) and glycated albumin (GA) effects were investigated in GLUT4, synapsin-1 (SYN1), tyrosine hydroxylase (TH), synaptophysin (SYP) proteins, and respective genes; NFKB binding activity in the SLC2A4 promoter; effects of increased histone acetylation grade by histone deacetylase 3 (HDAC3) inhibition. Hippocampal neurons (CA4 area) of obese+DM subjects displayed reduced GLUT4 expression and neuronal soma area, associated with increased expression of NFKB (p65). Challenges with TNF and GA decreased the SLC2A4/GLUT4 expression in SH-SY5Y neurons. TNF decreased SYN1, TH, and SYP mRNAs and respective proteins, and increased NFKB binding activity in the SLC2A4 promoter. Inhibition of HDAC3 increased the SLC2A4 expression and the total neuronal content of CRE-binding proteins (CREB/ICER), and also counterbalanced the repressor effect of TNF upon these parameters. This study revealed reduced postmortem human hippocampal GLUT4 content and neuronal soma area accompanied by increased proinflammatory activity in the brains of DM subjects. In isolated human neurons, inflammatory activation by TNF reduced not only the SLC2A4/GLUT4 expression but also the expression of some genes related to neuronal function (SYN1, TH, SYP). These effects may be related to epigenetic regulations (H3Kac and H4Kac status) since they can be counterbalanced by inhibiting HDAC3. These results uncover the improvement in GLUT4 expression and/or the inhibition of HDAC3 as promising therapeutic targets to fight DM-related neurodegeneration.
  • article 0 Citação(ões) na Scopus
    Apolipoprotein E genotypes were not associated with intracranial atherosclerosis: a population-based autopsy study br
    (2023) PARADELA, Regina Silva; FARIAS-ITAO, Daniela Souza; LEITE, Renata E. P.; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; NASLAVSKY, Michel Satya; ZATZ, Mayana; NITRINI, Ricardo; JACOB-FILHO, Wilson; SUEMOTO, Claudia Kimie
    Background: Apolipoprotein E gene (APOE) 64 allele is associated with a higher risk of carotid atherosclerosis, but less is known about the association of APOE with intracranial atherosclerotic disease (IAD). We aimed to investigate the association of APOE alleles with IAD in a cross-sectional autopsy study.Methods: We measured the stenosis in the 12 arteries of the Circle of Willis using postmortem morphometric measurements. The APOE polymorphism was determined by real-time polymerase chain reaction. We assessed the association between APOE polymorphism and IAD using regression models adjusted for sociodemographic and clinical variables. We also verified the modifier effect of age, sex, and race on this association. We stratified the analysis by age group to investigate the possibility of attrition bias.Results: In 400 participants (mean age = 73.2 +/- 12.3 years old, 51% female, and 64% White), IAD was evaluated in 4,504 artery segments. APOE- 64 was not associated with IAD nor with the number of artery stenosis compared to non-APOE- 64 carriers. Sociodemographic variables did not modify this relationship. Among participants older than 70 years, there was a trend towards an association between APOE allele 64 and a lower stenosis index in the middle cerebral artery, suggesting attrition bias related to the APOE- 64 effect on mortality.Conclusions: APOE alleles were not associated with IAD in this population-based autopsy study. Lower stenosis in older participants suggests the possibility of attrition bias.
  • article 0 Citação(ões) na Scopus
    Impact of oral health on frailty syndrome in frail older adults
    (2023) VENDOLA, Maria Cecilia Ciaccio; JACOB-FILHO, Wilson
    Objective: This study aimed to correlate oral and general health in frail and non-frail older adults. Methods: This observational study included 52 older adults, of whom 35 were frail (Frail Group), and 17 were non-frail (Non-Frail Group), according to Fried's self-reported test addressing oral health variables, number of systemic diseases, and medications in use. The geriatric oral health assessment index was used to assess the oral hygiene of the groups. Results: The number of preserved teeth in dentulous older adults was significantly higher in the Non-Frail Group (p=0.048). No significant differences were observed between the two groups in the use of dental prostheses or in the detection of soft tissue lesions. Overall, 74.3% of the Frail Group had a ""bad"" geriatric oral health index score, which significantly differed from that of the Non-Frail Group (p=0.045). The numbers of systemic diseases and medicines used were higher in the Frail Group than in the Non-Frail Group (p<0.001), demonstrating the pathophysiological characteristics of multimorbidity and polypharmacy in frailty syndrome. Conclusion: The results showed a clear correlation between oral and general health conditions and frailty syndrome.
  • article 0 Citação(ões) na Scopus
    Apolipoprotein E 62 allele is associated with lower risk of carotid artery obstruction in a population-based autopsy study
    (2023) PARADELA, Regina Silva; FARIAS-ITAO, Daniela Souza; LEITE, Renata E. P.; PASQUALUCCI, Carlos A.; GRINBERG, Lea T.; NASLAVSKY, Michel Satya; ZATZ, Mayana; NITRINI, Ricardo; JACOB-FILHO, Wilson; SUEMOTO, Claudia Kimie
    Introduction: Apolipoprotein E (APOE) 64 allele has been associated with higher carotid atherosclerosis risk, while the APOE-62 seems to decrease this risk. Data from autopsy studies, where carotid arteries can be evaluated in their full extension, is scarce. Therefore, we investigated the association between APOE alleles and direct morphometric measurements of carotid atherosclerosis in an autopsy study with an admixed sample.Methods: We measured the intima-media thickness (IMT) and stenosis of the common (CCA) and internal carotid (ICA) arteries. The APOE polymorphisms were determined by real-time polymerase chain reaction. Participants were classified into three groups according to the APOE alleles (62, 63, and 64). We evaluated the association between APOE groups and carotid atherosclerosis using adjusted regression models and included interaction terms of APOE alleles with age, sex, and race. Results: We evaluated 1,850 carotid artery samples from 185 participants (mean age=75 & PLUSMN;12 years old, 55% female, and 71% White). The APOE-62 group (n=17) had a lower carotid obstruction and a lower number of severe stenoses (& GE; 70%). Having at least one 64 allele (n=51) was not associated with carotid atherosclerosis. APOE alleles were also not associated with carotid IMT. Age, sex, and race did not modify these relationships.Conclusion: APOE-62 carriers had a lower percentage of carotid obstruction and less severe stenosis. APOE-64 was not related to a higher risk of carotid atherosclerosis in this cross-sectional population-based autopsy study.
  • article 0 Citação(ões) na Scopus
    Ten years of a geriatric oncology service at a public university cancer centre in Brazil
    (2023) KARNAKIS, Theodora; KANAJI, Ana L.; GATTAS-VERNAGLIA, Isabella F.; ADRIAZOLA, Izabela; RAMOS, Paola; LIMA, Maria Eduarda P. L. S.; ALMEIDA, Olga L. S.; JACOB-FILHO, Wilson; FERRIOLLI, Eduardo
    The implementation of a geriatric oncology service is challenging in both high-income and low-and-middle-income countries. The Octavio Frias de Oliveira Institute of Cancer of Sao Paulo (ICESP) is a tertiary healthcare complex of the Clinics Hospital of the Uni-versity of Sao Paulo Medical School and is considered a model of excellence in oncology in Latin America. The objective of this manuscript is to describe 10 years of the geriatric oncology service at ICESP and the challenges for its implementation. We performed a narrative description of the ICESP's geriatric oncology service and a general retrospective descriptive analysis of data collected from routine structured medical records of patients referred to the service from 2011 to 2021. This article highlights the different settings in which the service operates (outpatient, pre-operative and hospital follow-up). In this period, 1,700 patients were assessed for preoperative evaluation (median age 83.9, SD 4.95), 468 patients were evaluated for therapeutic decision (median age 79.4, SD 7.38), 968 in general geriatric oncology care outpatient clinics from 2012 to 2021 (median age 78.7, SD 7.91) and 1,391 inpatient evaluations. In the past 10 years, our geriatric oncol-ogy team has grown exponentially and changed its characteristics in order to adjust them to the hospital demands, raising awareness among the oncology teams about the benefit of using geriatric assessment and promoting multidisciplinary discussions.