Publications by authors named "Antonio Carlos Dos Santos"

89 Publications

Feasibility of intravoxel incoherent motion in the assessment of tumor microvasculature and blood-brain barrier integrity: a case-based evaluation of gliomas.

MAGMA 2021 Dec 15. Epub 2021 Dec 15.

InBrain Lab, FFCLRP, University of Sao Paulo, Ribeirao Preto, SP, 14040-900, Brazil.

Objective: To evaluate the feasibility of intravoxel incoherent motion (IVIM) in assessing blood-brain barrier (BBB) integrity and microvasculature in tumoral tissue of glioma patients.

Methods: Images from 8 high-grade and 4 low-grade glioma patients were acquired on a 3 T MRI scanner. Acquisition protocol included pre- and post-contrast T1- and T2-weighted imaging, FLAIR, dynamic susceptibility contrast (DSC), and susceptibility-weighted imaging (SWI). In addition, IVIM was acquired with 15 b-values and fitted under the non-negative least square (NNLS) model to output the diffusion (D) and pseudo-diffusion (D*) coefficients, perfusion fraction (f), and f times D* (fD*) maps.

Results: IVIM perfusion-related maps were sensitive to (1) blood flow and perfusion alterations within the microvasculature of brain tumors, in agreement with intra-tumoral susceptibility signal (ITSS); (2) enhancing areas of BBB breakdown in agreement with DSC maps as well as areas of BBB abnormality that was not detected on DSC maps; (3) enhancing perfusion changes within edemas; (4) detecting early foci of increased perfusion within low-grade gliomas.

Conclusion: The results suggest IVIM may be a promising approach to delineate tumor extension and progression in size, and to predict histological grade, which are clinically relevant information that characterize tumors and guide therapeutic decisions in patients with glioma.
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http://dx.doi.org/10.1007/s10334-021-00987-0DOI Listing
December 2021

Hippocampal Atrophy/Sclerosis Is Associated with Old, Calcified Parenchymal Brain Neurocysticercosis, But Not with More Recent, Viable Infections.

Am J Trop Med Hyg 2021 Oct 25;106(1):215-218. Epub 2021 Oct 25.

Center for Global Health, Department of Microbiology, Universidad Peruana Cayetano Heredia, Lima, Peru.

Magnetic resonance images from 197 patients with calcified neurocysticercosis (NCC), 38 with viable NCC and 197 NCC-free healthy rural villagers were evaluated to compare the frequency of hippocampal atrophy/sclerosis (HAS) across these populations. Scheltens' medial temporal atrophy scale was used for hippocampal rating. The median age of the 432 study participants was 46 years (interquartile range, 29-62 years), and 58% were women. Hippocampal atrophy/sclerosis was disclosed in 26.9% patients with calcified NCC, compared with 7.9% in patients with viable NCC and 8.1% in healthy rural villagers. After adjusting for age, gender, and history of epilepsy, hippocampal atrophy/sclerosis was more frequent in patients with calcified NCC than in those with viable cysts (RR, 3.60; 95% CI, 1.18- 0.99; P = 0.025) and healthy rural villagers (RR, 3.43; 95% CI, 1.94-6.06; P < 0.001), suggesting that hippocampal damage develops late in the course of this parasitic disease.
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http://dx.doi.org/10.4269/ajtmh.21-0392DOI Listing
October 2021

Meat Quality of Nellore Young Bulls-Effects of Different Days on Feed and Zilpaterol Hydrochloride Supplementation.

Animals (Basel) 2021 Sep 14;11(9). Epub 2021 Sep 14.

Department of Animal Science, Luiz de Queiroz College of Agriculture, University of São Paulo, Piracicaba 13418-900, SP, Brazil.

Ninety-six Nellore young bulls were fed (90 or 117 day) diets containing ZH (8.33 mg/kg) for 0, 20, 30, or 40 days to evaluate the effects of days on feed (DOF) and length of zilpaterol hydrochloride (ZH) supplementation on meat quality. At the end of feeding period, animals were slaughtered, and samples of the Longissimus muscle were collected to evaluate the chemical composition, fatty acid profile, color stability, shear force, and sensory profile. DOF did not affect chemical composition, shear force, sensory tenderness, and most of fatty acids; however, animals fed for 90 d had lower redness ( < 0.01), sustained juiciness ( < 0.01), and more flavor ( = 0.03) than those fed for 117 d. The ZH supplementation decreased lipid content and redness ( < 0.01), initial and sustained tenderness ( < 0.01), initial and sustained juiciness ( < 0.01), but increased protein ( < 0.01) and shear force ( < 0.01) as compared to non-supplemented animals. The ZH supplementation increased total PUFA, c9,c12-18:2, and 20:4-n6, and decreased c9-20:1 ( < 0.05). Feeding ZH impairs meat quality attributes of Nellore young bulls, regardless of duration of supplementation, while DOF has a small effect on meat quality properties.
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http://dx.doi.org/10.3390/ani11092688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467322PMC
September 2021

Epidemiological features of meningiomas: a single Brazilian center's experience with 993 cases.

Arq Neuropsiquiatr 2021 08;79(8):705-715

Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Patologia, Ribeirão Preto SP, Brazil.

Background: Meningiomas are the most frequent primary central nervous system (CNS) tumors. Their geographical and ethnic characteristics need to be known, in order to enable rational treatment.

Objective: To investigate clinical and epidemiological aspects in a series of patients with meningiomas.

Methods: Retrospective analysis on the demographic profile, location and histopathology of 993 patients with meningiomas (768 operated and 225 not operated).

Results: Meningiomas represented 43.8% of the primary CNS tumors; 6.8% were multiple tumors (14.7% with neurofibromatosis 2) and 0.6% were radiation-induced tumors. The mean ages were 53.0 and 63.9 years for operated and non-operated patients and the female/male ratios were 3.2:1 and 6.3:1. Diagnosis was made later among females. The peak incidences were in the 6th and 7th decades respectively for operated and non-operated patients. The incidence was low at early ages and higher among patients aged 70+ years. The meningiomas were intracranial in 96.5% and most were WHO grade I (88.9%) and transitional. In the spinal canal (3.5%), they occurred mainly in the dorsal region (all grade I; mostly transitional). The racial distribution was 1.0% in Asian-Brazilians, 87% in Caucasians and 12% in African-Brazilians. 83.4% and 51.6% of the patients were estimated to be recurrence-free at 10 and 20 years, and the mortality rate was 3%.

Conclusions: Most of the demographic data were similar to what has been observed in other western centers. Differences were higher incidence of meningiomas, female and older predominance in non-operated patients, predominance in Caucasian, and higher association with neurofibromatosis 2.
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http://dx.doi.org/10.1590/0004-282X-ANP-2020-0441DOI Listing
August 2021

Clinical and Biochemical Features of Hypopituitarism Among Brazilian Children With Zika Virus-Induced Microcephaly.

JAMA Netw Open 2021 05 3;4(5):e219878. Epub 2021 May 3.

Department of Pediatrics, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil.

Importance: The Zika virus infects progenitor neuron cells, disrupts cerebral development, and, in mice, drives hypothalamic defects. Patients with microcephaly caused by congenital Zika infection present with midline cerebral defects, which may result in hypopituitarism.

Objective: To analyze postnatal growth and the presence of clinical and biochemical features associated with hypopituitarism in children with congenital Zika infections.

Design, Setting, And Participants: In this prospective cohort study at 2 public referral hospitals in Bahia, Brazil, specializing in the treatment of congenital Zika infection, clinical data and growth parameters of 65 patients with the infection were evaluated. Data were analyzed from April 2017 through July 2018.

Exposure: Congenital Zika infection.

Main Outcomes And Measures: Length, weight, and head circumference were measured at birth and during follow up (ie, at 27 months of life) for each patient. Basal levels of free thyroxine, thyrotropin, cortisol, corticotropin, prolactin, insulin-like growth factor 1, insulin-like growth factor binding protein 3, urine and plasma osmolality, electrolytes, glucose, and insulin were evaluated at the age of 26 months to 28 months. All patients underwent central nervous system computed tomography scans and ophthalmic and otoacoustic evaluations at the time of this investigation or had done so previously.

Results: Among 65 patients (38 [58.4%] male; median [interquartile range] age at enrollment, 27 [26-28] months), 61 patients presented with severe brain defects (93.8%), including corpus callosum agenesis or hypoplasia (ie, midline brain defects; 25 patients [38.5%]) and optic nerve atrophy (38 patients [58.5%]). Most patients presented with severe neurodevelopmental delay (62 of 64 patients [96.9%]). Past or present clinical signs of hypopituitarism were rare, occurring in 3 patients (4.6%). Severe microcephaly, compared with mild or moderate microcephaly, was associated with a shorter length by median (interquartile range) z score at birth (-1.9 [-2.5 to -1.0] vs -0.3 [-1.0 to 0]; P < .001), but this difference did not persist at 27 months (-1.6 [-2.3 to -0.3] vs -2.9 [-4.0 to -1.2]; P = .06). Growth hormone deficiency or hypothyroidism were not observed in any patients, and glucose and insulin levels were within reference ranges for all patients. Low cortisol levels (ie, below 3.9 µg/dL) were observed in 4 patients (6.2%). These 4 patients presented with low (ie, below 7.2 pg/mL) or inappropriately low (ie, below 30 pg/mL) corticotropin levels. Low corticotropin levels (ie, below 7.2 pg/mL) were observed in 6 patients (9.2%). Diabetes insipidus was evaluated in 21 patients; it was confirmed in 1 patient (4.8%) and suggested in 3 patients (14.3%).

Conclusions And Relevance: This study found that congenital Zika infection with microcephaly was associated with midline brain defects and optic nerve atrophy. Children with congenital Zika infections presented with prenatal growth impairments with a lack of postnatal catch-up, as shown by persistent short length from birth until 27 months; these impairments were not associated with growth hormone deficiency. Patients also presented with severe developmental delay that was not associated with hypothyroidism, while central adrenal insufficiency and diabetes insipidus occurred in some patients.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.9878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120328PMC
May 2021

Treatment of distal unruptured intracranial aneurysms using a surface-modified flow diverter under prasugrel monotherapy: a pilot safety trial.

J Neurointerv Surg 2021 Jul 25;13(7):647-651. Epub 2021 Feb 25.

Division of Interventional Neuroradiology, Department of Medical Imaging, Hematology and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil

Background: Flow diverters (FDs) are effective in the treatment of carotid aneurysms. Compared with carotid aneurysms, the treatment of distal intracranial aneurysms with FDs has been associated with a relatively high incidence of complications. Low thrombogenic modified-surface FDs may reduce ischemic complications and allow for the use of a single antiplatelet medication. The aim of this study was to assess the safety and efficacy of the p48 MW HPC Flow Modulation Device (Phenox GmbH, Bochum, Germany) to treat distal intracranial aneurysms used in combination with prasugrel monotherapy.

Methods: This was a single-center, prospective, pivotal, open, single-arm study. Patients were included in this study from December 2019 to September 2020. The primary endpoints were the incidence of any neurologic deficit after treatment until 1 month of follow-up, defined as National Institutes of Health Stroke Scale (NIHSS) ≥1, and the incidence of acute ischemic lesions in magnetic resonance imagin (MRI) images 48 hours after treatment. The secondary endpoint was the rate of complete occlusion of the aneurysms at the 1-month follow-up.

Results: Twenty-one patients harboring 27 distal aneurysms of the anterior circulation were included. Mean age was 57.8 (SD 9.7) years, and 16 patients were female (80%). No patient had neurologic symptoms at the 1-month follow-up. Four patients (20%) had asymptomatic acute brain ischemic lesions on MRI. Complete aneurysm occlusion occurred in 9/27 (33.3%) aneurysms at the 1-month follow-up.

Conclusion: In this pilot safety trial, treatment of distal intracranial aneurysms with p48 MW HPC under monotherapy with prasugrel appeared to be safe.
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http://dx.doi.org/10.1136/neurintsurg-2020-017262DOI Listing
July 2021

Histological correlates of hippocampal magnetization transfer images in drug-resistant temporal lobe epilepsy patients.

Neuroimage Clin 2020 8;28:102463. Epub 2020 Oct 8.

Department of Neurosciences and Behavioral Sciences, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil. Electronic address:

Objective: Temporal lobe epilepsy patients (TLE) often present with hippocampal atrophy, increased T2 relaxation, and reduced magnetization transfer ratio (MTR) in magnetic resonance images (MRI). The histological correlates of the reduced hippocampal MTR are so far unknown. Since MTR is dependent on the tissue's macromolecules, our aim was to evaluate the correlations between cellular populations, extracellular matrix molecules and the MTR in TLE patients.

Methods: Patients with TLE (n = 26) and voluntaries (=20) were scanned in a 3 Tesla MRI scanner, and MTR images were calculated from 3DT1 sequences with magnetization pulse on resonance. Immunohistochemistry for neurons, reactive astrocytes, activated microglia, and extracellular matrix chondroitin sulfate were performed in formalin fixed, paraffin embedded tissues of TLE and autopsy controls (n = 10). Results were considered significant with adjusted p < 0.05.

Results: Compared to the respective controls, TLE patients had reduced hippocampal MTR, increased reactive astrocytes and activated microglia, increased extracellular chondroitin sulfate, and reduced neuron density, compares to controls. MTR correlated positively with neuron density in CA3 and with chondroitin sulfate in CA3 and CA1. Multiple linear regressions reinforced the correlations between chondroitin sulfate and MTR.

Significance: Our data indicate that extracellular matrix molecules are the most significant histological correlates of magnetization transfer ratio in the hippocampus of TLE patients.
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http://dx.doi.org/10.1016/j.nicl.2020.102463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7586233PMC
June 2021

Acute optic nerve lesions in first-ever NMOSD-related optic neuritis using conventional brain MRI: A Latin American multicenter study.

Mult Scler Relat Disord 2020 Nov 2;46:102558. Epub 2020 Oct 2.

Centro de Esclerosis Múltiple de Buenos Aires (CEMBA), Buenos Aires, Argentina.

Background: Few studies regarding MRI-defined acute optic nerve lesions (aONL) in patients with first-ever neuromyelitis optica spectrum disorder (NMOSD)-related optic neuritis (ON) have been reported worldwide and none of them was conducted in Latin America (LATAM). Therefore, we aimed to assess the frequency of aONL at disease onset using conventional brain MRI in LATAM.

Methods: We reviewed the medical records and brain MRIs (≤30 days from ON onset) of patients with ON as first lifetime NMOSD attack. Patients from Argentina (n=48), Ecuador (n=24), Brazil (n=22), Venezuela (n=10) and Mexico (n=8) were included, and further divided into two subgroups according to either presence (P-MRI) or absence (A-MRI) of aONL (T2 hyperintensity and/or contrast enhancement). Clinical, paraclinical, imaging and prognostic data were compared.

Results: A total of 112 patients were included and aONL were found in 86 (76.7%) at disease onset. Aquaporin-4 antibodies were detected in 69.6%. Non-Caucasian patients comprised 59.8% of the total cohort. In P-MRI, conventional brain MRI showed isolated or combined unilateral (54.4%, [8.5% of these aONL were associated with chiasmatic lesions]) and bilateral (46.6%, [35.9% of these aONL were associated with chiasmatic lesions]) lesions. Thus, 100% of chiasmatic lesions were associated with unilateral or bilateral lesions. No statistically significant differences were found in age, gender, ethnicity, clinical course, mean follow-up time, disability, and spinal cord MRI findings. However, rituximab use was higher in P-MRI than in A-MRI (p=0.006).

Conclusions: More than three quarters of LATAM patients with first-ever NMOSD-related ON have aONL detected by brain MRI. Unilateral lesions were the most common finding. Further studies including different ethnicities are needed to assess the generalizability of our results.
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http://dx.doi.org/10.1016/j.msard.2020.102558DOI Listing
November 2020

Age-related assessment of diffusion parameters in specific brain tracts correlated with cortical thinning.

Neurol Sci 2021 May 4;42(5):1799-1809. Epub 2020 Sep 4.

InBrain Lab, Department of Physics, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirao Preto, Sao Paulo, Brazil.

The aging process is associated with many brain structural alterations. These changes are not associated with neuronal loss but can be due to cortical structural changes that may be related to white matter (WM) structural alterations. In this study, we evaluated age-related changes in WM and gray matter (GM) parameters and how they correlate for specific brain tracts in a cohort of 158 healthy individuals, aged between 18 and 83 years old. In the tract-cortical analysis, cortical regions connected by tracts demonstrated similar thinning patterns for the majority of tracts. Additionally, a significant relationship was found between mean cortical thinning rate with fractional anisotropy (FA) and mean diffusivity (MD) alteration rates. For all tracts, age was the main effect controlling diffusion parameter alterations. We found no direct correlations between cortical thickness and FA or MD, except for in the fornix, for which the subcallosal gyrus thickness was significantly correlated to FA and MD (p < 0.05 FDR corrected). Our findings lead to the conclusion that alterations in the WM diffusion parameters are explained by the aging process, also associated with cortical thickness changes. Also, the alteration rates of the structural parameters are correlated to the different brain tracts in the aging process.
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http://dx.doi.org/10.1007/s10072-020-04688-9DOI Listing
May 2021

Contrast optimization in arterial spin labeling with multiple post-labeling delays for cerebrovascular assessment.

MAGMA 2021 Feb 3;34(1):119-131. Epub 2020 Sep 3.

Instituto de Física de São Carlos, Universidade de São Paulo, Av. Trabalhador São-Carlense, 400, São Carlos, SP, 13566-590, Brazil.

Objective: Improving the readout for arterial spin labeling with multiple post-labeling delays (multi-PLD ASL) through a flip angle (FA) sweep towards increasing contrast-to-noise ratio for long PLD images.

Methods: Images were acquired from 20 healthy subjects and 14 patients with severe, asymptomatic carotid artery stenosis (ACAS) in a 3T MRI scanner. Multi-PLD ASL images with conventional and proposed (FA sweep) readouts were acquired. For patients, magnetic resonance angiography was used to validate the multi-PLD ASL results. Perfusion values were calculated for brain regions irrigated by the main cerebral arteries and compared by analysis of variance.

Results: For healthy subjects, better contrast was obtained for long PLDs when using the proposed multi-PLD method compared to the conventional. For both methods, no hemispheric difference of perfusion was observed. For patients, the proposed method facilitated the observation of delayed tissue perfusion, which was not visible for long PLD using the conventional multi-PLD ASL.

Conclusion: We successfully assessed brain perfusion of patients with asymptomatic CAS using multi-PLD ASL with FA sweep. We were able to show subtle individual differences. Moreover, prolonged arterial transit time in patients was observed, although they were considered asymptomatic, suggesting that it may not be an adequate term to characterize them.
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http://dx.doi.org/10.1007/s10334-020-00883-zDOI Listing
February 2021

Evaluating H3F3A K27M and G34R/V somatic mutations in a cohort of pediatric brain tumors of different and rare histologies.

Childs Nerv Syst 2021 02 7;37(2):375-382. Epub 2020 Aug 7.

Department of Pediatrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Avenida Bandeirantes, 3900, Bloco G, 1 Andar, Ribeirão Preto, SP, 14049-900, Brazil.

Purpose: Somatic mutations on H3 histone are currently considered a genetic hallmark for midline pediatric high-grade gliomas (HGGs). Yet, different tumor histologies have been occasionally described to carry these mutations. Since histone modifications can lead to major epigenetic changes with direct impact on prognosis and treatment, we thought to investigate the occurrence of H3F3A K27M and G34R/V mutations in a cohort of pediatric tumors which included HGGs, low-grade gliomas, ependymomas, medulloblastomas, and a series of rare brain tumor lesions of different histologies.

Methods: A total of 82 fresh-frozen pediatric brain tumor samples were evaluated. PCR or RT-PCR followed by Sanger sequencing for the exon 2 of H3F3A (containing both K27 and G34 hotspots) were obtained and aligned to human genome. Loss of trimethylation mark (H3K27me3) in H3F3A/K27M-mutant samples was confirmed by immunohistochemistry.

Results: We found H3F3A/K27M mutation in 2 out of 9 cases of HGGs; no H3F3A/K27M mutations were detected in low-grade gliomas (27), ependymomas (n = 10), medulloblastomas (n = 21), or a series of rare pediatric brain tumors which included meningiomas, dysembryoplastic neuroepithelial tumors (DNETs), central nervous system (CNS) germ-cell tumors, choroid plexus tumors, cortical hamartoma, subcortical tubers, and schwannomas (n = 15). H3F3A/G34R/V mutation was not observed in any of the samples.

Conclusions: Our investigation reinforces the low frequency of H3F3A somatic mutations outside the HGG setting. Interestingly, an atypical focal brainstem glioma carrying H3F3A K27M mutation that showed protracted clinical course with late-onset tumor progression was identified.
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http://dx.doi.org/10.1007/s00381-020-04852-8DOI Listing
February 2021

Effect of using a nitrogen atmosphere on enzyme hydrolysis at high corn stover loadings in an agitated reactor.

Biotechnol Prog 2020 11 21;36(6):e3059. Epub 2020 Aug 21.

Laboratory of Renewable Resources Engineering, Purdue University, West Lafayette, Indiana, USA.

A comprehensive review of the literature shows that enzyme hydrolysis efficiency decreases with increased solids loadings at constant enzyme:cellulose ratios for pretreated lignocellulosic substrates. In seeking a mechanistic explanation for this phenomenon, we found that a nitrogen atmosphere enhances enzyme hydrolysis and minimizes the decrease in glucose yields as solids loadings are increased in an agitated bioreactor. For liquid hot water pretreated corn stover, at solids loadings of both 100 and 200 g/L and hydrolyzed for 72 hr in a 1 L bioreactor at pH 5.0 with 3.6 mg protein per g biomass, glucose yields were 55% in a nitrogen atmosphere versus 45% in air with agitation and about 34% without agitation. While mixing promotes biomass/enzyme contact and disperses sugars released during hydrolysis that would otherwise cause product inhibition, nitrogen gas displaces air, avoiding deactivation of cellulases by oxygen. The nitrogen effect points to a facile approach of enhancing hydrolysis at high solids loadings.
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http://dx.doi.org/10.1002/btpr.3059DOI Listing
November 2020

Brain magnetic resonance imaging features in multiple sclerosis and neuromyelitis optica spectrum disorders patients with or without aquaporin-4 antibody in a Latin American population.

Mult Scler Relat Disord 2020 Jul 14;42:102049. Epub 2020 Mar 14.

Servicio de Neurología, Hospital Italiano de Buenos Aires, Argentina, Gascón 450, Buenos Aires C 1181 Argentina.

Introduction: There is scarce evidence comparing the behavior in magnetic resonance (MRI) between positive and negative aquaporin-4 antibody neuromyelitis optica spectrum disorders (P-NMOSD and NNMOSD, respectively). The aim of this study was to describe and compare MRI features through a quantitative and qualitative analysis between P-NMOSD and NNMOSD patients in a cohort from Latin American (LATAM) patients.

Methods: We retrospectively reviewed the MRI and medical records of NMOSD patients as defined by the 2015 validated diagnostic criteria, and with at least 3 years of follow-up from disease onset (first symptom). We included patients from Argentina, Brazil and Venezuela. To be included, NMOSD patients must have had AQP4-ab status measured by a cell-based assay. Brain MRIs were obtained for each participant at disease onset and every 12 months for 3 years. Demographics, clinical and MRI variables (T2 lesion volume [T2LV], lesion distribution, cortical thickness [CT] and percentage of brain volume loss [PBVL]) were analyzed and compared between groups (P-NMOSD; NNMOSD) at disease onset and follow-up. A multiple sclerosis (MS) control group of patients was also included.

Results: We included 24 P-NMOSD, 15 NNMOSD and 35 MS patients. No differences in age, gender and follow-up time were observed between groups. Nor were differences found in lesion distribution at disease onset or in brain volumes during follow-up between P-NMOSD and NNMOSD patients (T2LV = 0.43, CT = 0.12, PBVL p = 0.45). Significant differences were observed in lesion distribution at disease onset, as well as in brain volumes during follow-up between NMOSD and MS (T2LV = p<0.001, CT = p<0.001, PBVL p = 0.01).

Conclusion: Different MRI features were observed between MS and NMOSD. However, no quantitative nor qualitative differences were observed between P-NMOSD and NNMOSD, not allowing us to differentiate NMOSD conditions by MRI.
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http://dx.doi.org/10.1016/j.msard.2020.102049DOI Listing
July 2020

Impact of epilepsy surgery on quality of life and burden of caregivers in children and adolescents.

Epilepsy Behav 2020 05 19;106:106961. Epub 2020 Mar 19.

Department of Neurosciences and Behavioural Sciences, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Center for Epilepsy Surgery (CIREP), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. Electronic address:

Objective: The objective of this study was to analyze the impact of pediatric epilepsy surgery on the quality of life (QOL), determining whether patients improve, worsen, or maintain their preoperative patterns, as it relates to the burden of caregivers, as well as evaluating potential related factors, from both the children and caregivers perspectives.

Material And Methods: This is a retrospective study of children and adolescents who underwent epilepsy surgery and were evaluated through clinical data, videoelectroencephalogram (V-EEG), neuroimaging findings, neuropsychological testing, and aspects of QOL. These assessments were performed prior to surgery and after six months and two years of follow-up. Quality of life was assessed with epilepsy-specialized questionnaires, namely Questionnaire health-related quality of life for children with epilepsy (QVCE-50), Autoquestionnaire Qualité de Vie Enfant Image Scale (AUQUEI), Quality of life in epilepsy inventory for adolescents (QOLEI-AD-48); and burden of caregivers with Burden Interview - ZARIT scale. Postoperative changes in QVCE-50 were quantified using measures of the analysis of variance (ANOVA MR) for comparison of the difference between the three times of the scale and domains.

Results: Fifty patients were enrolled. Of these, 27 (54%) were male, with a mean age at surgery of 8.2 years (range: 1-18 years). Thirty-five patients (70%) were Engel I and one was Engel II (2%) at six months of follow-up, whereas 28 (56%) were Engel I and 32 (64%) were Engel I or II at two years of follow-up. Preoperatively, 21 (42%) presented with moderate or severe intellectual disability. Postoperative cognitive evaluations at the two-year follow-up showed 18 (36%) maintained similar deficits. The QVCE-50 showed postoperative improvement in the two-year follow-up period, but not at six months after surgery. Postoperative improvements were associated mainly with better seizure outcome. Autoperception evaluations were limited because of the clinical and cognitive severity of patients. The burden of caregivers was quoted as mild to moderate and remained unchanged postoperatively.

Conclusions: Children and adolescents with surgically treated epilepsy reach a good seizure outcome, stabilize in intellectual and adaptive functions, and have an increase in QOL, from the caregiver's perspective. Nevertheless, their burden remains unchanged. Seizure outcome is the main factor for improvement in the QOL. The upgrading of structured questionnaires and QOL instruments specific to pediatric epilepsy can be helpful to assess patient- and caregiver-reported surgical outcomes, allowing for better planning of therapeutic approaches.
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http://dx.doi.org/10.1016/j.yebeh.2020.106961DOI Listing
May 2020

Clinical features and prognosis of late-onset neuromyelitis optica spectrum disorders in a Latin American cohort.

J Neurol 2020 May 13;267(5):1260-1268. Epub 2020 Jan 13.

Centro de Esclerosis Múltiple de Buenos Aires, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

Background: We aimed to assess the clinical, paraclinical, imaging and prognostic features of patients with late-onset neuromyelitis optica spectrum disorder (LO-NMOSD; ≥ 50 years at disease onset) LO-NMOSD, compared with early onset-NMOSD (EO-NMOSD, ≤ 49 years at disease onset), in Latin American (LATAM).

Methods: We retrospectively reviewed the medical records of patients with NMOSD, as defined using the 2015 validated diagnostic criteria. We included patients from Argentina, Brazil and Venezuela. They were divided into: LO-NMOSD and EO-NMOSD and comparison among the groups were performed.

Results: Among these 140 NMOSD patients, 24 (17.1%) were LO-NMOSD; 64% were positive for aquaporin-4 antibodies; and 41.5% of this population cohort was non-Caucasian. Severe disability [expanded disability status scale (EDSS) ≥ 6] at the last follow-up and presence of comorbidities were significantly associated with LO-NMOSD, compared with EO-NMOSD. LO-NMOSD patients had a shorter median time to EDSS ≥ 4 than EO-NMOSD patients (46 vs. 60 months; log-rank test p = 0.0006). Furthermore, we observed a positive correlation between age at onset and EDSS score at the last follow-up (Spearman r = 0.34, p < 0.0001).

Conclusion: LO-NMOSD patients from LATAM developed early severe disability, compared with EO-NMOSD. Therefore, age at onset could have important implications for the long-term prognosis of NMOSD patients.
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http://dx.doi.org/10.1007/s00415-020-09699-2DOI Listing
May 2020

Multimodal quantitative magnetic resonance imaging analysis with individualized postprocessing in patients with drug-resistant focal epilepsy and conventional visual inspection negative for epileptogenic lesions.

Clinics (Sao Paulo) 2019 22;74:e908. Epub 2019 Jul 22.

Divisao de Neurorradiologia, Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, BR.

Objectives: Approximately one-third of candidates for epilepsy surgery have no visible abnormalities on conventional magnetic resonance imaging. This is extremely discouraging, as these patients have a less favorable prognosis. We aimed to evaluate the utility of quantitative magnetic resonance imaging in patients with drug-resistant neocortical focal epilepsy and negative imaging.

Methods: A prospective study including 46 patients evaluated through individualized postprocessing of five quantitative measures: cortical thickness, white and gray matter junction signal, relaxation rate, magnetization transfer ratio, and mean diffusivity. Scalp video-electroencephalography was used to suggest the epileptogenic zone. A volumetric fluid-attenuated inversion recovery sequence was performed to aid visual inspection. A critical assessment of follow-up was also conducted throughout the study.

Results: In the subgroup classified as having an epileptogenic zone, individualized postprocessing detected abnormalities within the region of electroclinical origin in 9.7% to 31.0% of patients. Abnormalities outside the epileptogenic zone were more frequent, up to 51.7%. In five patients initially included with negative imaging, an epileptogenic structural abnormality was identified when a new visual magnetic resonance imaging inspection was guided by information gleaned from postprocessing. In three patients, epileptogenic lesions were detected after visual evaluation with volumetric fluid-attenuated sequence guided by video electroencephalography.

Conclusion: Although quantitative magnetic resonance imaging analyses may suggest hidden structural lesions, caution is warranted because of the apparent low specificity of these findings for the epileptogenic zone. Conversely, these methods can be used to prevent visible lesions from being ignored, even in referral centers. In parallel, we need to highlight the positive contribution of the volumetric fluid-attenuated sequence.
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http://dx.doi.org/10.6061/clinics/2019/e908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636588PMC
April 2020

Brain and spinal MRI features distinguishing MS from different AQP4 antibody serostatus NMOSD at disease onset in a cohort of Latin American patients.

Mult Scler 2020 07 24;26(8):945-954. Epub 2019 May 24.

Centro de Esclerosis Múltiple de Buenos Aires (CEMBA), Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

Objective: We aimed to evaluate magnetic resonance imaging (MRI) previously used criteria (Matthews's criteria, MC) for differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disorders (NMOSD) in Caucasian and non-Caucasian populations (Argentina, Brazil and Venezuela) with positive (P-NMOSD), negative (N-NMOSD), and unknown (U-NMOSD) aquaporin-4 antibody serostatus at disease onset and to assess the added diagnostic value of spinal cord MRI in these populations.

Methods: We reviewed medical records, and MRIs were assessed by two blinded evaluators and were scored using MC. Short-segment transverse myelitis (STM) was added as a new criterion. MC sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined.

Results: We included 282 patients (MS = 188 and NMOSD = 94). MC applied to the entire cohort showed 97.8% sensitivity, 82.9% specificity, 92.0% PPV, and 95.1% NPV for differentiating MS from NMOSD. A subanalysis applied only to non-Caucasian (MS = 89 and NMOSD = 47) showed 100% sensitivity, 80.8% specificity, 90.8% PPV, and 100% NPV. Similar sensitivity, specificity, PPV, and NPV of MC for MS versus P-NMOSD ( = 55), N-NMOSD ( = 28), and U-NMOSD ( = 21) were observed.

Conclusion: MC distinguished MS from NMOSD of all serostatus in a Latin American cohort that included non-Caucasian populations. Addition of STM to MC did not raise the accuracy significantly.
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http://dx.doi.org/10.1177/1352458519849517DOI Listing
July 2020

Urbanicity and risk of first-episode psychosis: incidence study in Brazil.

Br J Psychiatry 2019 12;215(6):726-729

Professor, Department of Preventive Medicine, Faculty of Medicine, University of São Paulo; and Director, Population Mental Health Research Centre, University of São Paulo, Brazil.

We estimated the incidence of first-episode psychosis over a 3-year period in a Brazilian catchment area comprising the region's main city, Ribeirão Preto (1 425 306 persons-years at risk), and 25 other municipalities with a total of 1 646 556 persons-years at risk. The incidence rates were estimated and adjusted by gender and age, using the direct standardisation method to the world population as reference. The incidence of psychosis was higher in the younger groups, men, and among Black and minority ethnic Brazilians. Psychosis incidence was lower in Ribeirão Preto (16.69/100 000 person-years at risk; 95% CI 15.68-17.70) compared with the average incidence in the remaining municipalities (21.25/100 000 person-years at risk; 95% CI 20.20-22.31), which have lower population density, suggesting a distinct role for urbanicity in the incidence of first-episode psychosis in low- and middle-income countries.
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http://dx.doi.org/10.1192/bjp.2019.110DOI Listing
December 2019

Manual Hippocampal Subfield Segmentation Using High-Field MRI: Impact of Different Subfields in Hippocampal Volume Loss of Temporal Lobe Epilepsy Patients.

Front Neurol 2018 20;9:927. Epub 2018 Nov 20.

Department of Neurosciences and Behavioral Sciences, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.

In patients with temporal lobe epilepsy (TLE), presurgical magnetic resonance imaging (MRI) often reveals hippocampal atrophy, while neuropathological assessment indicates the different types of hippocampal sclerosis (HS). Different HS types are not discriminated in MRI so far. We aimed to define the volume of each hippocampal subfield on MRI manually and to compare automatic and manual segmentations for the discrimination of HS types. The T2-weighted images from 14 formalin-fixed age-matched control hippocampi were obtained with 4.7T MRI to evaluate the volume of each subfield at the anatomical level of the hippocampal head, body, and tail. Formalin-fixed coronal sections at the level of the body of 14 control cases, as well as tissue samples from 24 TLE patients, were imaged with a similar high-resolution sequence at 3T. Presurgical three-dimensional (3D) T1-weighted images from TLE went through a FreeSurfer 6.0 hippocampal subfield automatic assessment. The manual delineation with the 4.7T MRI was identified using Luxol Fast Blue stained 10-μm-thin microscopy slides, collected at every millimeter. An additional section at the level of the body from controls and TLE cases was submitted to NeuN immunohistochemistry for neuronal density estimation. All TLE cases were classified according to the International League Against Epilepsy's (ILAE's) HS classification. Manual volumetry in controls revealed that the dentate gyrus (DG)+CA4 region, CA1, and subiculum accounted for almost 90% of the hippocampal volume. The manual 3T volumetry showed that all TLE patients with type 1 HS (TLE-HS1) had lower volumes for DG+CA4, CA2, and CA1, whereas those TLE patients with HS type 2 (TLE-HS2) had lower volumes only in CA1 ( ≤ 0.038). Neuronal cell densities always decreased in CA4, CA3, CA2, and CA1 of TLE-HS1 but only in CA1 of TLE-HS2 ( ≤ 0.003). In addition, TLE-HS2 had a higher volume ( = 0.016) and higher neuronal density ( < 0.001) than the TLE-HS1 in DG + CA4. Automatic segmentation failed to match the manual or histological findings and was unable to differentiate TLE-HS1 from TLE-HS2. Total hippocampal volume correlated with DG+CA4 and CA1 volumes and neuronal density. For the first time, we also identified subfield-specific pathology patterns in the manual evaluation of volumetric MRI scans, showing the importance of manual segmentation to assess subfield-specific pathology patterns.
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http://dx.doi.org/10.3389/fneur.2018.00927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6256705PMC
November 2018

Lignin-Enzyme Interactions in the Hydrolysis of Lignocellulosic Biomass.

Trends Biotechnol 2019 05 23;37(5):518-531. Epub 2018 Nov 23.

Laboratory of Renewable Resources Engineering, Purdue University, West Lafayette, IN 47907, USA; Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; www.purdue.edu/LORRE. Electronic address:

Lignin is central to overcoming recalcitrance in the enzyme hydrolysis of lignocellulose. While the term implies a physical barrier in the cell wall structure, there are also important biochemical components that direct interactions between lignin and the hydrolytic enzymes that attack cellulose in plant cell walls. Progress toward a deeper understanding of the lignin synthesis pathway - and the consistency between a range of observations over the past 40 years in the very extensive literature on cellulose hydrolysis - is resulting in advances in reducing a major impediment to cellulose conversion: the cost of enzymes. This review addresses lignin and its role in the hydrolysis of hardwood and other lignocellulosic residues.
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http://dx.doi.org/10.1016/j.tibtech.2018.10.010DOI Listing
May 2019

Acupuncture at ST36 exerts neuroprotective effects via inhibition of reactive astrogliosis in infantile rats with hydrocephalus.

Acupunct Med 2018 12 24;36(6):386-393. Epub 2018 Aug 24.

Department of Surgery and Anatomy, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

Background: Acupuncture has been associated with improved cerebral circulation, analgesia, neuromodulatory function and neurogenesis. In particular, acupuncture at ST36 has been widely used in several central nervous system (CNS) disorders, including neurodegenerative diseases. However, its effects on hydrocephalus have not been studied. Our aim was to evaluate the effects of acupuncture at ST36 on behaviour, motor development and reactive astrogliosis in infantile rats with hydrocephalus.

Methods: Hydrocephalus was induced in sixteen 7-day-old pup rats by injection of 20% kaolin into the cisterna magna. One day after hydrocephalus induction, acupuncture was applied once daily (for 30 min) for a total of 21 days in eight randomly selected animals (HAc group) while the remaining eight remained untreated (H group). An additional eight healthy animals were included as controls (C group). All animals were weighed daily and, from the fifth day after hydrocephalus induction, underwent MRI to determine the ventricular ratio (VR). Rats were also exposed to modified open-field tests every 3 days until the end of the experiment. After 21 days all the animals were euthanased and their brains removed for histology and immunohistochemistry.

Results: Hydrocephalic rats showed an increase in VR when compared with control rats (P<0.01). In addition, these animals exhibited delayed weight gain, which was attenuated with acupuncture treatment. Hydrocephalic animals treated with acupuncture performed better in open field tests (P<0.05), and had a reduction in reactive astrocyte cell density in the corpus callosum and external capsule, as assessed by GFAP (glial fibrillary acidic protein) immunohistochemistry (P<0.05).

Conclusions: These findings indicate that acupuncture at ST36 has a neuroprotective potential mediated, in part, by inhibition of astrogliosis.
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http://dx.doi.org/10.1136/acupmed-2017-011515DOI Listing
December 2018

Monitoring optic chiasmatic-hypothalamic glioma volumetric changes by MRI in children under clinical surveillance or chemotherapy.

Childs Nerv Syst 2019 01 4;35(1):63-72. Epub 2018 Aug 4.

Division of Radiology, Department of Clinics, University Hospital of Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, 14049-900, Brazil.

Purpose: Optic pathway gliomas represent 5% of pediatric brain tumors and are typically low-grade lesions. Because of their unpredictable clinical course, adequate treatment approaches have been controversial, involving surveillance, surgery, chemotherapy, and radiotherapy. In this study, we use volumetric imaging to compare evolution of optic chiasmatic-hypothalamic gliomas (OCHG) treated with and without chemotherapy, analyzing tumor volume variation during the overall period.

Methods: A total of 45 brain MRI were retrospectively analyzed for 14 patients with OCHG. Volumetric assessment of the lesions was performed by a neuroradiologist, using software DISPLAY. OCHG patients were allocated into two groups: group 1 (n = 8) who underwent chemotherapy and group 2 (n = 6) who did not receive chemotherapy. Outcome analysis was performed comparing tumor volume evolution of these two groups.

Results: The results showed a reduction of 4.4% of the volume of the lesions for group 1 after the end of chemotherapy, with an increase of 5.3% in volume in the late follow-up examination. For group 2, we found a slight reduction (5%) of the overall volume of the lesions, both with no statistical significance (p > 0.05).

Conclusions: From the limited series analyzed in this study, no significant differences were observed in relation to the volume change of lesions treated or not treated with chemotherapy. Larger prospective clinical trials are needed to better evaluate the effect of chemotherapy and radiological response of OCHG.
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http://dx.doi.org/10.1007/s00381-018-3904-9DOI Listing
January 2019

Correlations between changes in the hypothalamic-pituitary-adrenal axis and neurochemistry of the anterior cingulate gyrus in postpartum depression.

J Affect Disord 2018 10 10;239:274-281. Epub 2018 Jul 10.

Departments of Neuroscience and Behavior, Ribeirão Preto Medical School, University of São Paulo, Av. dos Bandeirantes, 3900, Ribeirão Preto, SP 14049-900, Brazil.

Background: This study aimed to investigate associations between indicators of hypothalamic-pituitary-adrenal axis (HPA) functioning and metabolite levels in the anterior cingulate gyrus (ACG) of women with postpartum depression (PPD).

Methods: The sample (mean age = 28.5 ± 4.6 years) consisted of 20 women with PPD and 19 postpartum euthymic (PPE) women. Brain metabolites were quantified by proton magnetic resonance spectroscopy (H-MRS). Salivary cortisol samples were collected upon awakening and 30 min and 12 h later, at 20.6 ± 6.6 (PPD) and 23.0 ± 7.4 (PPE) weeks after childbirth.

Results: There were no significant differences between groups in respect to metabolite levels in the ACG. Compared with PPE, PPD women had less diurnal variation (DVr%). In the PPD group, positive correlations were found between DVr% and myo-inositol (mI/Cr) levels, and between cortisol awakening response (CARi%) and glutamate + glutamine (Glx/Cr) levels. The correlation between CARi% and Glx/Cr remained significant even after controlling for the interval, in weeks, from birth and MR spectroscopy and to hormonal data collection, and the use of contraceptives.

Limitations: The limitations of the study include the small sample size and the use of oral contraceptives by around half of the sample.

Conclusions: In the remote postpartum period (mean 21.8 ± 6.9 weeks) and in the presence of depressive episodes, the decreased responsiveness of the HPA axis after awakening and a smaller decrease in cortisol levels over the day were associated with lower levels of metabolites in the ACG. These results may contribute to the development of biological models to explain the etiology of PPD.
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http://dx.doi.org/10.1016/j.jad.2018.07.028DOI Listing
October 2018

Magnetic resonance imaging: dynamic contrast enhancement and diffusion-weighted imaging to identify malignant cervical lymph nodes.

Radiol Bras 2018 Mar-Apr;51(2):71-75

MD, PhD, Professor of Neuroradiology, Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP-USP), Ribeirão Preto, SP, Brazil.

Objective: To examine the potential of two magnetic resonance imaging (MRI) techniques-dynamic contrast enhancement (DCE) and diffusion-weighted imaging (DWI)-for the detection of malignant cervical lymph nodes.

Materials And Methods: Using DCE and DWI, we evaluated 33 cervical lymph nodes. For the DCE technique, the maximum relative enhancement, relative enhancement, time to peak enhancement, wash-in rate, wash-out rate, brevity of enhancement, and area under the curve were calculated from a semi-quantitative analysis. For the DWI technique, apparent diffusion coefficients (ADCs) were acquired in the region of interest of each lymph node. Cystic or necrotic parts were excluded. All patients underwent neck dissection or node biopsy. Imaging results were correlated with the histopathological findings. None of the patients underwent neoadjuvant treatment before neck dissection.

Results: Relative enhancement, maximum relative enhancement, and the wash-in rate were significantly higher in malignant lymph nodes than in benign lymph nodes ( < 0.009; < 0.05; and < 0.03, respectively). The time to peak enhancement was significantly shorter in the malignant lymph nodes ( < 0.02). In the multivariate analysis, the variables identified as being the most capable of distinguishing between benign and malignant lymph nodes were time to peak enhancement (sensitivity, 73.7%; specificity, 69.2%) and relative enhancement (sensitivity, 89.2%; specificity, 69.2%).

Conclusion: Although DCE was able to differentiate between benign and malignant lymph nodes, there is still no consensus regarding the use of a semi-quantitative analysis, which is difficult to apply in a clinical setting. Low ADCs can predict metastatic disease, although inflammatory processes might lead to false-positive results.
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http://dx.doi.org/10.1590/0100-3984.2017.0005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935398PMC
May 2018

Neurofunctional changes after a single mirror therapy intervention in chronic ischemic stroke.

Int J Neurosci 2018 Oct 20;128(10):966-974. Epub 2018 Mar 20.

a Brain Institute/Onofre Lopes University Hospital, Federal University of Rio Grande Do Norte (UFRN) , Natal-RN , Brazil.

Background: Mirror therapy (MT) is becoming an alternative rehabilitation strategy for various conditions, including stroke. Although recent studies suggest the positive benefit of MT in chronic stroke motor recovery, little is known about its neural mechanisms.

Purpose: To identify functional brain changes induced by a single MT intervention in ischemic stroke survivors, assessed by both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI).

Materials And Methods: TMS and fMRI were used to investigate 15 stroke survivors immediately before and after a single 30-min MT session.

Results: We found statistically significant increase in post-MT motor evoked potential (MEP) amplitude (increased excitability) from the affected primary motor cortex (M1), when compared to pre-MT MEP. Post-MT fMRI maps were associated with a more organized and constrained pattern, with a more focal M1 activity within the affected hemisphere after MT, limited to the cortical area of hand representation. Furthermore, we find a change in the balance of M1 activity toward the affected hemisphere. In addition, significant correlation was found between decreased fMRI β-values and increased MEP amplitude post-MT, in the affected hemisphere.

Conclusion: Our study suggests that a single MT intervention in stroke survivors is related to increased MEP of the affected limb, and a more constrained activity of the affected M1, as if activity had become more constrained and limited to the affected hemisphere.
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http://dx.doi.org/10.1080/00207454.2018.1447571DOI Listing
October 2018

Temperature dependent cellulase adsorption on lignin from sugarcane bagasse.

Bioresour Technol 2018 Mar 20;252:143-149. Epub 2017 Dec 20.

Laboratory of Renewable Resources Engineering, Purdue University, West Lafayette, IN, USA; Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN, USA. Electronic address:

Extents of adsorption of cellulolytic enzymes on lignin, derived from sugarcane bagasse, were an inverse function of incubation temperature and varied with type of lignin extraction. At 45 °C, lignin derived from acid hydrolyzed liquid hot water pretreated bagasse completely adsorbed cellulolytic enzymes from Trichoderma reesei within 90 min. Lignin derived from enzyme hydrolyzed liquid hot water pretreated bagasse adsorbed only 60% of T. reesei endoglucanase, exoglucanase and β-glucosidase activities. β-Glucosidase from Aspergillus niger was not adsorbed. At 30 °C, adsorption of all of the enzymes was minimal and enzyme hydrolysis at 30 °C approached that at 45 °C after 168 h. Hence, temperature provided an approach to decrease loss of enzyme activity by reducing enzyme adsorption on lignin. This helps to explain why simultaneous saccharification and fermentation (SSF) and consolidated bioprocessing (CBP), both carried out at 30-32 °C, could offer viable options for mitigating lignin-derived inhibition effects.
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http://dx.doi.org/10.1016/j.biortech.2017.12.061DOI Listing
March 2018

Burkitt-like lymphoma of the brain mimicking an intraventricular colloid cyst.

Radiol Bras 2017 Nov-Dec;50(6):413-414

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), Ribeirão Preto, SP, Brazil.

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http://dx.doi.org/10.1590/0100-3984.2016.0065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746893PMC
January 2018

Deactivation and activation of lignocellulose degrading enzymes in the presence of laccase.

Enzyme Microb Technol 2018 Feb 19;109:25-30. Epub 2017 Sep 19.

Department of Biochemistry and Molecular Biology, BIOAGRO, Federal University of Viçosa, Viçosa, MG 36.570-000, Brazil.

Cellulase and hemicellulase activities in a 1:1 ratio of enzymes extracted from Chrysoporthe cubensis and Penicillium pinophilum were evaluated in the presence of known monocomponent phenolic inhibitors and also with phenol mixtures derived from alkali pretreated sugarcane bagasse. The cellulolytic activities from C. cubensis:P. pinophilum displayed a much higher tolerance to phenolic inhibitors than equivalent enzyme activities obtained from Trichoderma reesei and Aspergillus niger. Enzymes from T. reesei and A. niger were deactivated at 0.3 and 1.5mg phenols/mg protein, respectively, as reported previously, while enzymes from C. cubensis:P. pinophilum resisted deactivation at 35mg phenols/mg protein. However, tolerance of xylanase with respect to phenols required the presence of laccase. Removal of laccase (enzyme) activity using sodium azide resulted in a 2x higher xylanase deactivation (from 40% to 80%). This paper identifies enzymes that are phenol tolerant, and whose adoption for lignocellulose hydrolysis could contribute to reductions in enzyme loading needed to hydrolyze alkali pretreated lignocellulosic substrates in the presence of lignin derived phenols.
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http://dx.doi.org/10.1016/j.enzmictec.2017.09.007DOI Listing
February 2018

Perineural spread of malignant head and neck tumors: review of the literature and analysis of cases treated at a teaching hospital.

Radiol Bras 2017 Sep-Oct;50(5):323-327

PhD, Radiologist at the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), Ribeirão Preto, SP, Brazil.

Perineural tumor spread refers to the migration of tumor cells along nerve tissues. It worsens the prognosis, increases the recurrence rate, and diminishes 5-year survival by up to 30%. It is an important finding on imaging tests employed in the staging of patients with head and neck cancers, because it cannot be assessed by the surgeon alone. Nevertheless, it is frequently overlooked. In this study, we reviewed the literature regarding the imaging and pathophysiological aspects of this type of dissemination. We also analyzed ten imaging tests, obtained from a teaching hospital in Brazil, in which there were radiological signs of perineural tumor spread.
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http://dx.doi.org/10.1590/0100-3984.2015.0215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656073PMC
November 2017

Understanding the association of neurocysticercosis and mesial temporal lobe epilepsy and its impact on the surgical treatment of patients with drug-resistant epilepsy.

Epilepsy Behav 2017 11 24;76:168-177. Epub 2017 Apr 24.

CIREP, Centro de Cirurgia de Epilepsia, Faculdade de Medicina, Universidade de São Paulo, Ribeirão Preto, Brazil.

Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is one of the most common types of focal epilepsies. This is an epileptic syndrome commonly associated with treatment-resistant seizures, being also the most prevalent form of drug-resistant epilepsy which is treated surgically in most epilepsy surgery centers. Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system, and one of the most common etiological agents of focal epilepsy, affecting millions of patients worldwide. Recently, researchers reported a curious association between MTLE-HS with NCC, but this association remains poorly understood. Some argue that calcified NCC lesions in MTLE-HS patients is only a coincidental finding, since both disorders are prevalent worldwide. However, others suppose there might exist a pathogenic relationship between both disorders and some even suspect that NCC, by acting as an initial precipitating injury (IPI), might cause hippocampal damage and, eventually, MTLE-HS. In this review, we discuss the various reports that examine this association, and suggest possible explanations for why calcified NCC lesions are also observed in patients with MTLE-HS. We also propose mechanisms by which NCC could lead to MTLE-HS. Finally, we discuss the implications of NCC for the treatment of pharmacologically-resistant focal epilepsies in patients with calcified NCC or in patients with MTLE-HS and calcified NCC lesions. We believe that investigations in the relationship between NCC and MTLE-HS might offer further insights into how NCC may trigger epilepsy, and into how MTLE-HS originates. Moreover, observations in patients with drug-resistant epilepsy with both NCC and hippocampal sclerosis may not only aid in the understanding and treatment of patients with MTLE-HS, but also of patients with other forms of dual pathologies aside from NCC. This article is part of a Special Issue titled Neurocysticercosis and Epilepsy.
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http://dx.doi.org/10.1016/j.yebeh.2017.02.030DOI Listing
November 2017
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