JOSE MARCELO FARFEL
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Ortopediae Traumatologia, Faculdade de Medicina - Docente
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
LIM/22 - Laboratório de Patolologia Cardiovascular, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
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- Comprehensive geriatric assessment predicts mortality and adverse outcomes in hospitalized older adults(2014) AVELINO-SILVA, Thiago J.; FARFEL, Jose M.; CURIATI, Jose A. E.; AMARAL, Jose R. G.; CAMPORA, Flavia; JACOB-FILHO, WilsonBackground: Comprehensive Geriatric Assessment (CGA) provides detailed information on clinical, functional and cognitive aspects of older patients and is especially useful for assessing frail individuals. Although a large proportion of hospitalized older adults demonstrate a high level of complexity, CGA was not developed specifically for this setting. Our aim was to evaluate the application of a CGA model for the clinical characterization and prognostic prediction of hospitalized older adults. Methods: This was a prospective observational study including 746 patients aged 60 years and over who were admitted to a geriatric ward of a university hospital between January 2009 and December 2011, in Sao Paulo, Brazil. The proposed CGA was applied to evaluate all patients at admission. The primary outcome was in-hospital death, and the secondary outcomes were delirium, nosocomial infections, functional decline and length of stay. Multivariate binary logistic regression was performed to assess independent factors associated with these outcomes, including socio-demographic, clinical, functional, cognitive, and laboratory variables. Impairment in ten CGA components was particularly investigated: polypharmacy, activities of daily living (ADL) dependency, instrumental activities of daily living (IADL) dependency, depression, dementia, delirium, urinary incontinence, falls, malnutrition, and poor social support. Results: The studied patients were mostly women (67.4%), and the mean age was 80.5 +/- 7.9 years. Multivariate logistic regression analysis revealed the following independent factors associated with in-hospital death: IADL dependency (OR= 4.02; CI= 1.52-10.58; p= .005); ADL dependency (OR= 2.39; CI= 1.25-4.56; p= .008); malnutrition (OR= 2.80; CI= 1.63-4.83; p< .001); poor social support (OR= 5.42; CI= 2.93-11.36; p< .001); acute kidney injury (OR= 3.05; CI= 1.78-5.27; p< .001); and the presence of pressure ulcers (OR= 2.29; CI= 1.04-5.07; p= .041). ADL dependency was independently associated with both delirium incidence and nosocomial infections (respectively: OR= 3.78; CI= 2.30-6.20; p< .001 and OR= 2.30; CI= 1.49-3.49; p< .001). The number of impaired CGA components was also found to be associated with in-hospital death (p< .001), delirium incidence (p< .001) and nosocomial infections (p= .005). Additionally, IADL dependency, malnutrition and history of falls predicted longer hospitalizations. There were no significant changes in overall functional status during the hospital stay. Conclusions: CGA identified patients at higher risk of in-hospital death and adverse outcomes, of which those with functional dependence, malnutrition and poor social support were foremost.
- Repair of Oxidative DNA Damage, Cell-Cycle Regulation and Neuronal Death May Influence the Clinical Manifestation of Alzheimer's Disease(2014) SILVA, Aderbal R. T.; SANTOS, Ana Cecilia Feio; FARFEL, Jose M.; GRINBERG, Lea T.; FERRETTI, Renata E. L.; CAMPOS, Antonio Hugo Jose Froes Marques; CUNHA, Isabela Werneck; BEGNAMI, Maria Dirlei; ROCHA, Rafael M.; CARRARO, Dirce M.; PEREIRA, Carlos Alberto de Braganca; JACOB-FILHO, Wilson; BRENTANI, HelenaAlzheimer's disease (AD) is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles). Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX), DNA repair (p53, BRCA1, PTEN), and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p(27Kip1), phospho-Rb and E2F1) through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA) composed of three groups: I) ""clinical-pathological AD"" (CP-AD) - subjects with neuropathological AD (Braak >= IV and CERAD = B or C) and clinical dementia (CDR >= 2, IQCODE >= 3.8); II) ""pathological AD"" (P-AD) - subjects with neuropathological AD (Braak >= IV and CERAD = B or C) and without cognitive impairment (CDR 0, IQCODE < 3.2); and III) ""normal aging"" (N) - subjects without neuropathological AD (Braak <= II and CERAD 0 or A) and with normal cognitive function (CDR 0, IQCODE<3.2). Our results show that high levels of oxidative DNA damage are present in all groups. However, significant reductions in DNA repair and cell-cycle inhibition markers and increases in cell-cycle progression and cell death markers in subjects with CP-AD were detected when compared to both P-AD and N groups, whereas there were no significant differences in the studied markers between P-AD individuals and N subjects. This study indicates that, even in the setting of pathological AD, healthy cognition may be associated with a preserved repair to DNA damage, cell-cycle regulation, and cell death in post-mitotic neurons.
- LEARNING TO READ IN OLDER AGE IMPROVES COGNITIVE PERFORMANCE: FINDINGS FROM A PROSPECTIVE OBSERVATIONAL STUDY(2014) SILVA, Eduardo Marques da; APOLINARIO, Daniel; MAGALDI, Regina Miksian; BENNETT, David A.; NITRINI, Ricardo; JACOB FILHO, Wilson; FARFEL, Jose Marcelo
- Complex Network-Driven View of Genomic Mechanisms Underlying Parkinson's Disease: Analyses in Dorsal Motor Vagal Nucleus, Locus Coeruleus, and Substantia Nigra(2014) CORRADINI, Beatriz Raposo; IAMASHITA, Priscila; TAMPELLINI, Edilaine; FARFEL, Jose Marcelo; GRINBERG, Lea Tenenholz; MOREIRA-FILHO, Carlos AlbertoParkinson's disease (PD)-classically characterized by severe loss of dopaminergic neurons in the substantia nigra pars compactahas a caudal-rostral progression, beginning in the dorsal motor vagal nucleus and, in a less extent, in the olfactory system, progressing to the midbrain and eventually to the basal forebrain and the neocortex. About 90% of the cases are idiopathic. To study the molecular mechanisms involved in idiopathic PD we conducted a comparative study of transcriptional interaction networks in the dorsal motor vagal nucleus (VA), locus coeruleus (LC), and substantia nigra (SN) of idiopathic PD in Braak stages 4-5 (PD) and disease-free controls (CT) using postmortem samples. Gene coexpression networks (GCNs) for each brain region (patients and controls) were obtained to identify highly connected relevant genes (hubs) and densely interconnected gene sets (modules). GCN analyses showed differences in topology and module composition between CT and PD networks for each anatomic region. In CT networks, VA, LC, and SN hub modules are predominantly associated with neuroprotection and homeostasis in the ageing brain, whereas in the patient's group, for the three brain regions, hub modules are mostly related to stress response and neuron survival/degeneration mechanisms.
- Sexual Dimorphism in the Human Olfactory Bulb: Females Have More Neurons and Glial Cells than Males(2014) OLIVEIRA-PINTO, Ana V.; SANTOS, Raquel M.; COUTINHO, Renan A.; OLIVEIRA, Lays M.; SANTOS, Glaucia B.; ALHO, Ana T. L.; LEITE, Renata E. P.; FARFEL, Jose M.; SUEMOTO, Claudia K.; GRINBERG, Lea T.; PASQUALUCCI, Carlos A.; JACOB-FILHO, Wilson; LENT, RobertoSex differences in the human olfactory function reportedly exist for olfactory sensitivity, odorant identification and memory, and tasks in which odors are rated based on psychological features such as familiarity, intensity, pleasantness, and others. Which might be the neural bases for these behavioral differences? The number of cells in olfactory regions, and especially the number of neurons, may represent a more accurate indicator of the neural machinery than volume or weight, but besides gross volume measures of the human olfactory bulb, no systematic study of sex differences in the absolute number of cells has yet been undertaken. In this work, we investigate a possible sexual dimorphism in the olfactory bulb, by quantifying postmortem material from 7 men and 11 women (ages 55-94 years) with the isotropic fractionator, an unbiased and accurate method to estimate absolute cell numbers in brain regions. Female bulbs weighed 0.132 g in average, while male bulbs weighed 0.137 g, a non-significant difference; however, the total number of cells was 16.2 million in females, and 9.2 million in males, a significant difference of 43.2%. The number of neurons in females reached 6.9 million, being no more than 3.5 million in males, a difference of 49.3%. The number of non-neuronal cells also proved higher in women than in men: 9.3 million and 5.7 million, respectively, a significant difference of 38.7%. The same differences remained when corrected for mass. Results demonstrate a sex-related difference in the absolute number of total, neuronal and non-euronal cells, favoring women by 40-50%. It is conceivable that these differences in quantitative cellularity may have functional impact, albeit difficult to infer how exactly this would be, without knowing the specific circuits cells make. However, the reported advantage of women as compared to men may stimulate future work on sex dimorphism of synaptic microcircuitry in the olfactory bulb.