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229 result(s) for "de Souza, Leonardo C"
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Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer’s disease
Alzheimer’s disease (AD) is associated with memory impairment and altered peripheral metabolism. Mounting evidence indicates that abnormal signaling in a brain-periphery metabolic axis plays a role in AD pathophysiology. The activation of pro-inflammatory pathways in the brain, including the interleukin-6 (IL-6) pathway, comprises a potential point of convergence between memory dysfunction and metabolic alterations in AD that remains to be better explored. Using T2-weighted magnetic resonance imaging (MRI), we observed signs of probable inflammation in the hypothalamus and in the hippocampus of AD patients when compared to cognitively healthy control subjects. Pathological examination of post-mortem AD hypothalamus revealed the presence of hyperphosphorylated tau and tangle-like structures, as well as parenchymal and vascular amyloid deposits surrounded by astrocytes. T2 hyperintensities on MRI positively correlated with plasma IL-6, and both correlated inversely with cognitive performance and hypothalamic/hippocampal volumes in AD patients. Increased IL-6 and suppressor of cytokine signaling 3 (SOCS3) were observed in post-mortem AD brains. Moreover, activation of the IL-6 pathway was observed in the hypothalamus and hippocampus of AD mice. Neutralization of IL-6 and inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling in the brains of AD mouse models alleviated memory impairment and peripheral glucose intolerance, and normalized plasma IL-6 levels. Collectively, these results point to IL-6 as a link between cognitive impairment and peripheral metabolic alterations in AD. Targeting pro-inflammatory IL-6 signaling may be a strategy to alleviate memory impairment and metabolic alterations in the disease.
Visual neglect in posterior cortical atrophy
Background In posterior cortical atrophy (PCA), there is a progressive impairment of high-level visual functions and parietal damage, which might predict the occurrence of visual neglect. However, neglect may pass undetected if not assessed with specific tests, and might therefore be underestimated in PCA. In this prospective study, we aimed at establishing the side, the frequency and the severity of visual neglect, visual extinction, and primary visual field defects in an unselected sample of PCA patients. Methods Twenty-four right-handed PCA patients underwent a standardized battery of neglect tests. Visual fields were examined clinically by the confrontation method. Results Sixteen of the 24 patients (66%) had signs of visual neglect on at least one test, and fourteen (58%) also had visual extinction or hemianopia. Five patients (21%) had neither neglect nor visual field defects. As expected, left-sided neglect was more severe than right-sided neglect. However, right-sided neglect resulted more frequently in this population (29%) than in previous studies on focal brain lesions. Conclusion When assessed with specific visuospatial tests, visual neglect is frequent in patients with PCA. Diagnosis of neglect is important because of its negative impact on daily activities. Clinicians should consider the routine use of neglect tests to screen patients with high-level visual deficits. The relatively high frequency of right-sided neglect in neurodegenerative patients supports the hypothesis that bilateral brain damage is necessary for right-sided neglect signs to occur, perhaps because of the presence in the right hemisphere of crucial structures whose damage contributes to neglect.
Revising the definition of Alzheimer's disease: a new lexicon
Alzheimer's disease (AD) is classically defined as a dual clinicopathological entity. The recent advances in use of reliable biomarkers of AD that provide in-vivo evidence of the disease has stimulated the development of new research criteria that reconceptualise the diagnosis around both a specific pattern of cognitive changes and structural/biological evidence of Alzheimer's pathology. This new diagnostic framework has stimulated debate about the definition of AD and related conditions. The potential for drugs to intercede in the pathogenic cascade of the disease adds some urgency to this debate. This paper by the International Working Group for New Research Criteria for the Diagnosis of AD aims to advance the scientific discussion by providing broader diagnostic coverage of the AD clinical spectrum and by proposing a common lexicon as a point of reference for the clinical and research communities. The cornerstone of this lexicon is to consider AD solely as a clinical and symptomatic entity that encompasses both predementia and dementia phases.
Cognitive impairment in hoarding disorder: a systematic review
In the present study, we aimed to perform a systematic review evaluating the cognitive performance of patients with hoarding disorder (HD) compared with controls. We hypothesized that HD patients would present greater cognitive impairment than controls. A systematic search of the literature using the electronic databases MEDLINE, SCOPUS, and LILACS was conducted on May 2020, with no date limit. The search terms were \"hoarding disorder,\" \"cognition,\" \"neuropsychology,\" \"cognitive impairment,\" and \"cognitive deficit.\" We included original studies assessing cognitive functioning in patients with HD. We retrieved 197 studies initially. Of those, 22 studies were included in the present study. We evaluated 1757 patients who were 41 to 72 years old. All selected studies comprised case-control studies and presented fair quality. Contrary to our hypothesis, HD patients showed impairment only in categorization skills in comparison with controls, particularly at confidence to complete categorization tasks. Regarding attention, episodic memory, working memory, information-processing speed, planning, decision-making, inhibitory control, mental flexibility, language, and visuospatial ability, HD patients did not show impairment when compared with controls. There is a paucity of studies on social cognition in HD patients, although they may show deficits. The impact of emotion in cognition is also understudied in HD patients. Except for categorization skills, the cognitive performance in HD patients does not seem to be impaired when compared with that in controls. Further work is needed to explore social cognition and the impact of emotion in cognitive performance in HD patients.
Disinhibition in Frontotemporal Dementia and Alzheimer’s Disease: A Neuropsychological and Behavioural Investigation
Cognitive tests of inhibitory control show variable results for the differential diagnosis between behavioural variant of Frontotemporal Dementia (bvFTD) and Alzheimer's disease (AD). We compared the diagnostic accuracies of tests of inhibitory control and of a behavioural questionnaire, to distinguish bvFTD from AD. Three groups of participants were enrolled: 27 bvFTD patients, 25 AD patients, and 24 healthy controls. Groups were matched for gender, education, and socio-economic level. Participants underwent a comprehensive neuropsychological assessment of inhibitory control, including Hayling Test, Stroop, the Five Digits Test (FDT) and the Delay Discounting Task (DDT). Caregivers completed the Barratt Impulsiveness Scale 11th version (BIS-11). bvFTD and AD groups showed no difference in the tasks of inhibitory control, while the caregiver questionnaire revealed that bvFTD patients were significantly more impulsive (BIS-11: bvFTD 76.1+9.5, AD 62.9+13, p < .001). Neuropsychological tests of inhibitory control failed to distinguish bvFTD from AD. On the contrary, impulsivity caregiver-completed questionnaire provided good distinction between bvFTD and AD. These results highlight the current limits of cognitive measures of inhibitory control for the differential diagnosis between bvFTD and AD, whereas questionnaire information appears more reliable and in line with clinical diagnostics.
Fluorescence in situ hybridization analysis of endosymbiont genera reveals novel infection patterns in a tomato-infesting Bemisia tabaci population from Brazil
The Bemisia tabaci cryptic species complex harbors a diversified flora of primary and secondary endosymbionts, which plays crucial roles in many aspects of the insect biology. The endosymbiont infection pattern is dependent upon many factors, including host plant and geographic origin. In Brazil, the invasion of B. tabaci Middle East-Asia Minor-1 (MEAM 1) populations was observed in tomato (Solanum lycopersicum L.) fields in the 1990s, which was followed by severe begomovirus epidemics. Here we confirmed the vertical transmission of “Candidatus Portiera” and the localization of secondary endosymbionts in distinct B. tabaci developmental stages. Hamiltonella defensa was detected in bacteriocytes but also scattered in the leg muscles as well as in the male heads. Wolbachia-specific signals were found in eggs, nymphs, male adults, and female gonads in predominant association with bacteriocytes. These results were somewhat surprising since Wolbachia infection is rarely found in MEAM 1 populations from the Old World. Our results reinforce the notion that endosymbiont infection pattern may vary according to the insect population, gender, developmental stage, and geographic origin. This characterization will provide tools to study the endosymbiont function in the transmission ability/efficiency of a complex of tomato-infecting bipartite begomoviruses by B. tabaci under Neotropical conditions.
Effect of the Presence of Surfactants and Immobilization Conditions on Catalysts’ Properties of Rhizomucor miehei Lipase onto Chitosan
Lipase from Rhizomucor miehei (RML) was immobilized onto chitosan support in the presence of some surfactants added at low levels using two different strategies. In the first approach, the enzyme was immobilized in the presence of surfactants on chitosan supports previously functionalized with glutaraldehyde. In the second one, after prior enzyme adsorption on chitosan beads in the presence of surfactants, the complex chitosan beads-enzyme was then cross-linked with glutaraldehyde. The effects of surfactant concentrations on the activities of free and immobilized RML were evaluated. Hexadecyltrimethylammonium bromide (CTAB) promoted an inhibition of enzyme activity while the nonionic surfactant Triton X-100 caused a slight increase in the catalytic activity of the free enzyme and the derivatives produced in both methods of immobilization. The best derivatives were achieved when the lipase was firstly adsorbed on chitosan beads at 4 °C for 1 h, 220 rpm followed by cross-link the complex chitosan beads-enzyme with glutaraldehyde 0.6% v.v −1 at pH 7. The derivatives obtained under these conditions showed high catalytic activity and excellent thermal stability at 60° and 37 °C. The best derivative was also evaluated in the synthesis of two flavor esters namely methyl and ethyl butyrate. At non-optimized conditions, the maximum conversion yield for methyl butyrate was 89%, and for ethyl butyrate, the esterification yield was 92%. The results for both esterifications were similar to those obtained when the commercial enzyme Lipozyme® and free enzyme were used in the same reaction conditions and higher than the one achieved in the absence of the selected surfactant.
Spatial and temporal fluctuations in COVID-19 fatality rates in Brazilian hospitals
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Gamma variant of concern has spread rapidly across Brazil since late 2020, causing substantial infection and death waves. Here we used individual-level patient records after hospitalization with suspected or confirmed coronavirus disease 2019 (COVID-19) between 20 January 2020 and 26 July 2021 to document temporary, sweeping shocks in hospital fatality rates that followed the spread of Gamma across 14 state capitals, during which typically more than half of hospitalized patients aged 70 years and older died. We show that such extensive shocks in COVID-19 in-hospital fatality rates also existed before the detection of Gamma. Using a Bayesian fatality rate model, we found that the geographic and temporal fluctuations in Brazil’s COVID-19 in-hospital fatality rates were primarily associated with geographic inequities and shortages in healthcare capacity. We estimate that approximately half of the COVID-19 deaths in hospitals in the 14 cities could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization and pandemic preparedness are critical to minimize population-wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries. Analysis of individual-level patient records from Brazil reveals that the extensive shocks in COVID-19 mortality rates are associated with pre-pandemic geographic inequities as well as shortages in healthcare capacity during the pandemic.
Proteomic Analysis of a Rat Streptozotocin Model Shows Dysregulated Biological Pathways Implicated in Alzheimer’s Disease
Alzheimer’s Disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory loss and cognitive impairment, affecting 35 million individuals worldwide. Intracerebroventricular (ICV) injection of low to moderate doses of streptozotocin (STZ) in adult male Wistar rats can reproduce classical physiopathological hallmarks of AD. This biological model is known as ICV-STZ. Most studies are focused on the description of behavioral and morphological aspects of the ICV-STZ model. However, knowledge regarding the molecular aspects of the ICV-STZ model is still incipient. Therefore, this work is a first attempt to provide a wide proteome description of the ICV-STZ model based on mass spectrometry (MS). To achieve that, samples from the pre-frontal cortex (PFC) and hippocampus (HPC) of the ICV-STZ model and control (wild-type) were used. Differential protein abundance, pathway, and network analysis were performed based on the protein identification and quantification of the samples. Our analysis revealed dysregulated biological pathways implicated in the early stages of late-onset Alzheimer’s disease (LOAD), based on differentially abundant proteins (DAPs). Some of these DAPs had their mRNA expression further investigated through qRT-PCR. Our results shed light on the AD onset and demonstrate the ICV-STZ as a valid model for LOAD proteome description.
UV random laser emission from flexible ZnO-Ag-enriched electrospun cellulose acetate fiber matrix
We report an alternative random laser (RL) architecture based on a flexible and ZnO-enriched cellulose acetate (CA) fiber matrix prepared by electrospinning. The electrospun fibers, mechanically reinforced by polyethylene oxide and impregnated with zinc oxide powder, were applied as an adsorbent surface to incorporate plasmonic centers (silver nanoprisms). The resulting structures – prepared in the absence (CA-ZnO) and in the presence of silver nanoparticles (CA-ZnO-Ag) - were developed to support light excitation, guiding and scattering prototypes of a RL. Both materials were excited by a pulsed (5 Hz, 5 ns) source at 355 nm and their fluorescence emission monitored at 387 nm. The results suggest that the addition of silver nanoprisms to the ZnO- enriched fiber matrix allows large improvement of the RL performance due to the plasmon resonance of the silver nanoprisms, with ~80% reduction in threshold energy. Besides the intensity and spectral analysis, the RL characterization included its spectral and intensity angular dependences. Bending the flexible RL did not affect the spectral characteristics of the device. No degradation was observed in the random laser emission for more than 10,000 shots of the pump laser.