FT-MIR-ATR Associated with Chemometrics Methods: A Preliminary Analysis of Deterioration State of Brazil Nut Oil.

Brazil nut oil is highly valued in the food, cosmetic, chemical, and pharmaceutical industries, as well as other sectors of the economy. This work aims to use the Fourier transform infrared (FTIR) technique associated with partial least squares regression (PLSR) and principal component analysis (PCA) to demonstrate that these methods can be used in a prior and rapid analysis in quality control. Natural oils were extracted and stored for chemical analysis. PCA presented two groups regarding the state of degradation, subdivided into super-degraded and partially degraded groups in 99.88% of the explained variance. The applied PLS reported an acidity index (AI) prediction model with root mean square error of calibration (RMSEC) = 1.8564, root mean square error of cross-validation (REMSECV) = 4.2641, root mean square error of prediction (RMSEP) = 2.1491, R2cal (calibration correlation coefficient) equal to 0.9679, R2val (validation correlation coefficient) equal to 0.8474, and R2pred (prediction correlation coefficient) equal to 0, 8468. The peroxide index (PI) prediction model showed RMSEC = 0.0005, REMSECV = 0.0016, RMSEP = 0.00079, calibration R2 equal to 0.9670, cross-validation R2 equal to 0.7149, and R2 of prediction equal to 0.9099. The physical-chemical analyses identified that five samples fit in the food sector and the others fit in other sectors of the economy. In this way, the preliminary monitoring of the state of degradation was reported, and the prediction models of the peroxide and acidity indexes in Brazil nut oil for quality control were determined.

Fetal neurosurgery.

Among fetal surgical procedures, neurosurgery stands out due to the number of cases and the possibility of developing new procedures that can be performed in the fetal period. To perform fetal neurosurgical procedures, there is a need for specialized centers that have experts in the diagnosis of fetal pathologies and a highly complex obstetrics service with specialized maternal-fetal teams associated with a pediatric neurosurgery center with expertise in the diverse pathologies of the fetus and the central nervous system that offers multidisciplinary follow-up during postnatal life. Services that do not have these characteristics should refer their patients to these centers to obtain better treatment results. It is essential that the fetal neurosurgical procedure be performed by a pediatric neurosurgeon with extensive experience, as he will be responsible for monitoring these patients in the postnatal period and for several years. The objective of this manuscript is to demonstrate the diagnostic and treatment possibilities, in the fetal period, of some neurosurgical diseases such as hydrocephalus, tumors, occipital encephalocele, and myelomeningocele.

Crude Enzyme Concentrate of Filamentous Fungus Hydrolyzed Chitosan to Obtain Oligomers of Different Sizes.

Chitosan is a non-cytotoxic polysaccharide that, upon hydrolysis, releases oligomers of different sizes that may have antioxidant, antimicrobial activity and the inhibition of cancer cell growth, among other applications. It is, therefore, a hydrolysis process with great biotechnological relevance. Thus, this study aims to use a crude enzyme concentrate (CEC) produced by a filamentous fungus to obtain oligomers with different molecular weights. The microorganism was cultivated in a liquid medium (modified Czapeck-with carboxymethylcellulose as enzyme inducer). The enzymes present in the CEC were identified by LC-MS/MS, with an emphasis on cellobiohydrolase (E.C 3.2.1.91). The fungus of the Aspergillus genus was identified by amplifying the ITS1-5.8S-ITS2 rDNA region and metaproteomic analysis, where the excreted enzymes were identified with sequence coverage greater than 84% to A. nidulans. Chitosan hydrolysis assays compared the CEC with the commercial enzyme (Celluclast 1.5 L®). The ability to reduce the initial molecular mass of chitosan by 47.80, 75.24, and 93.26% after 2.0, 5.0, and 24 h of reaction, respectively, was observed. FTIR analyses revealed lower absorbance of chitosan oligomers' spectral signals, and their crystallinity was reduced after 3 h of hydrolysis. Based on these results, we can conclude that the crude enzyme concentrate showed a significant technological potential for obtaining chitosan oligomers of different sizes.

Impact of surgery on ambulatory status in patients with symptomatic neoplastic spinal cord compression in southern brazil / Impacto da cirurgia sobre a capacidade de ambulatória em pacientes com compressão neoplásica sintomática da medula espinalno sul do brasil / Impacto de la cirugía en la capacidad de ambulación en pacientes con compresión medular neoplásica sintomática en el sur de brasil

ABSTRACT Background: Spinal cord compression is a common complication of spine metastasis and multiple myeloma. About 30% of patients with cancer develop symptomatic spinal metastases during their illness. Prompt diagnosis and surgical treatment of these lesions, although palliative, are likely to reduce the morbidity and improve quality of life by improving ambulatory function. Study Design: Retrospective review of medical records. Objective: To evaluate postoperative functional recovery and the epidemiological profile of neoplastic spinal cord compression in two neurosurgical centers in southern Brazil. Methods: We retrospectively analyzed the data of all patients who underwent palliative surgery for symptomatic neoplastic spine lesion from metastatic cancer, in two neurosurgical centers, between January 2003 and July 2021. The variables age, sex, neurological status, histological type, affected segment, complications and length of hospitalization were analyzed. Results: A total of 82 patients were included. The lesions occurred in the thoracic spine in 60 cases. At admission, 95% of the patients had neurological deficits, most of which were Frankel C (37%). At histopathological analysis, breast cancer was the most common primary site. After surgery, the neurological status of 46 patients (56%) was reclassified according to the Frankel scale. Of these, 22 (47%) regained ambulatory capacity. Conclusion: Surgical treatment of metastatic spinal cord compression improved neurological status and ambulatory ability in our sample. Level of evidence II; Retrospective study.

RESUMO: Introdução: A compressão medular é uma complicação comum de metástases da coluna vertebral e de mieloma múltiplo. Cerca de 30% dos pacientes com câncer desenvolvem metástases sintomáticas na coluna no decorrer da doença. O diagnóstico imediato e o tratamento cirúrgico dessas lesões, embora paliativos, em geral reduzema morbidade e melhoram a qualidade de vidaao ampliar a capacidade de deambular. Desenho do estudo: Revisão retrospectiva de prontuários médicos. Objetivo: Avaliar a recuperação funcional pós-operatória e o perfil epidemiológico da compressão medular neoplásica em dois centros de neurocirurgia do sul do Brasil. Métodos: Analisamos retrospectivamente os dados de todos os pacientes submetidos à cirurgia paliativa de lesão neoplásica sintomática da coluna decorrente decâncer metastático, em dois centros neurocirúrgicos entre janeiro de 2003 e julho de 2021. Foram analisadas as variáveis idade, sexo, estado neurológico, tipo histológico, segmento acometido, complicações e tempo de internação. Resultados: Foram incluídos 82 pacientes no estudo. As lesões ocorreram na coluna torácica em 60 casos. À internação, 95% dos pacientes apresentavam déficits neurológicos, sendoa maioria classificada como Frankel C (37%). Na análise histopatológica, o câncer de mama foi o sítio primário mais comum. Depois da cirurgia, 46 pacientes (56%) tiveram o estado neurológico reclassificado pela escala de Frankel. Entre eles, 22 (47%) recuperaram a capacidade de deambular. Conclusões: O tratamento cirúrgico da compressão medular metastática melhorou o estado neurológico e a capacidade de deambulação em nossa amostra. Nível de evidência II; Estudo retrospectivo.

RESUMEN: Introducción: La compresión de la médula espinal es una complicación común de la metástasis de la columna vertebral y el mieloma múltiple. Aproximadamente el 30% de los pacientes con cáncer desarrollan metástasis espinales sintomáticas en el curso de la enfermedad. El diagnóstico precoz y el tratamiento quirúrgico de estas lesiones, aunque son paliativos, suelen reducir la morbilidad y mejor en lacalidad de vida al aumentar la de ambulación. Diseño del estudio: Revisión retrospectiva de registros médicos. Objetivo: Evaluarla recuperación funcional postoperatoria y el perfil epidemiológico de la compresión medular neoplásica en dos centros neuroquirúrgicos del sur de Brasil. Métodos: Analizamos retrospectivamente los datos de todos los pacientes sometidos a cirugía paliativa por lesión vertebral neoplásica sintomática por cáncer metastásico, en dos centros neuroquirúrgicos entre enero de 2003 y julio de 2021. Se analizaron las variables edad, sexo, estado neurológico, tipo histológico, segmento afectado, complicaciones y duración de la hospitalización. Resultados: Se incluyeron 82 pacientes en el estudio. Las lesiones se produjeron en la columna torácica en 60 casos. Al ingreso, el 95% de los pacientes presentaban déficits neurológicos y la mayoría de ellos eran clasificados como Frankel C (37%). En el análisis histopatológico, elcáncer de mama fue el sitio primario más común. Después de la cirugía, se reclasificó el estado neurológico de 46 pacientes (56%) por la escala de Frankel. Entre ellos, 22 (47%) recuperaron la capacidadde deambulación. Conclusiones: El tratamiento quirúrgico de la compresión medular metastásica mejoró el estado neurológico y la capacidad de deambulación en nuestra muestra. Nivel de evidencia II; Estudio retrospectivo.

Surgery versus radiotherapy: Long term outcomes of T1 glottic cancer.

AIM: The aim of this study was to compare the outcomes, patterns of failure and laryngeal preservation rates in patients with T1N0 glottic cancer treated with surgery or radiotherapy. MATERIALS/METHODS: Retrospective study of T1N0 glottic cancer patients treated in our institution between January 2007 and December 2017. Histologically proven squamous cell carcinoma patients, treated with upfront cordectomy/partial laryngectomy (S group) or radiotherapy (RT group) were included. Elective treatment of the neck was not permitted. Local failure (LF), disease-free survival (DFS), ultimate disease-free survival (UDFS), laryngectomy-free survival (LFS), disease-specific mortality (DSM) and overall survival (OS) were evaluated. RESULTS: Two hundred and one patients were eligible (172 S group, 29 RT group), with a median follow-up of 38.8 months. Overall, 33 (16%) patients had a recurrence, 30 (17%) in the S group and 3 (10%) in the RT group. Local failure was the predominant site of failure (28 S, 2 RT). Overall, of all those that were salvaged, 17 (8%) underwent total laryngectomy (15 S, 2 RT). There was no significant difference in the 5-year cumulative incidence of LF (20.8% S, 8.1% RT, p = 0.138), 5-y LFS (85.0% vs. 91.7%, p = 0.809), 5-y DFS (67.5% vs. 82.1%, p = 0.343), 5-y UDFS (82.5% vs. 90.3%, p = 0.647) and 5-y OS (84.5% vs. 90.3%, p = 0.892). Multivariate analysis showed no correlation between initial treatment and the analyzed outcomes. CONCLUSION: Primary surgery or radiotherapy were similar first line options, since they do not differ in all outcomes. Patients' and physician's preferences must be considered when choosing first treatment.

DNA repair and cell synthesis proteins: immunohistochemical expression and correlation with recurrence-regrowth in meningiomas.

Meningiomas are considered the second most common neoplasm of the central nervous system in adults. Most of them are benign with slow growth, frequent in women and with a high recurrence rate. In tumors, DNA error repair processes lose efficacy, providing mutagenesis and genomic instability. This work evaluated the expression of proteins involved in cell synthesis (cyclin D1) and DNA errors repair (MUTYH, XPF, XPG) in meningiomas, relating them to clinical, tumor and survival variables. The study included 85 patients, with a mean age of 52 ± 13.3 years and most of them women (2:1 ratio). Sixty-seven cases were grade I (79%). Grade II tumors were independent predictors of recurrence-regrowth (HR: 2.8; p = 0.038). The high expression of cyclin D1 was associated with grade II (p = 0.001) and low MUTYH expression with grade I (p = 0.04). Strong expression of XPF and XPG was associated with grade II (p = 0.002; p < 0.001) and with recurrence-regrowth (p = 0.04; p = 0.003). Strong XPF expression was significantly related to large tumors (p = 0.03). An association of cyclin D1, MUTYH and XPF were found. Survival was not associated with the expression of any of the proteins studied. To know the role of DNA repair proteins and cell synthesis is important for understanding the processes of origin and tumor development. Grade II meningiomas and strong expression of XPF and XPG were predictors of recurrence or regrowth and may assist in clinical management, considering the high recurrence of meningiomas and the absence of consensus regarding treatment.

Bruns Syndrome Caused by Intraventricular Neurocysticercosis: Literature Review

Bruns syndrome is one of the clinical presentations of intraventricular neurocysticercosis, and it is characterized by episodes of headache, vertigo and vomiting. The intraventricular form of neurocysticercosis occurs in 7% to 20% of the cases, and it is more serious than the intraparenchymal form. The management is primarily surgical, associated with pharmacological therapy with anthelmintic drugs and corticosteroids. We report the case of a patient who presented Bruns syndrome due to neurocysticercosis.

Organotypic slice culture model demonstrates inter-neuronal spreading of alpha-synuclein aggregates.

Here we describe the use of an organotypic hippocampal slice model for studying α-synuclein aggregation and inter-neuronal spreading initiated by microinjection of pre-formed α-synuclein fibrils (PFFs). PFF injection at dentate gyrus (DG) templates the formation of endogenous α-synuclein aggregates in axons and cell bodies of this region that spread to CA3 and CA1 regions. Aggregates are insoluble and phosphorylated at serine-129, recapitulating Lewy pathology features found in Parkinson's disease and other synucleinopathies. The model was found to favor anterograde spreading of the aggregates. Furthermore, it allowed development of slices expressing only serine-129 phosphorylation-deficient human α-synuclein (S129G) using an adeno-associated viral (AAV) vector in α-synuclein knockout slices. The processes of aggregation and spreading of α-synuclein were thereby shown to be independent of phosphorylation at serine-129. We provide methods and highlight crucial steps for PFF microinjection and characterization of aggregate formation and spreading. Slices derived from genetically engineered mice or manipulated using viral vectors allow testing of hypotheses on mechanisms involved in the formation of α-synuclein aggregates and their prion-like spreading.

Assessment of Anthropometric and Physical Health Indicators before and after Pituitary Surgery in Patients with Nonfunctioning Pituitary Adenomas, Acromegaly, and Cushing Disease.

INTRODUCTION: Individuals with pituitary adenomas may have organic consequences of their disease or therapy, and psychological changes can compromise their quality of life (QoL). This study aimed to determine the anthropometric profile and health indicators of patients with pituitary adenoma before and after pituitary surgery. METHODS: Forty-four patients were included in this study. Out of these, 22 patients had nonfunctioning adenomas (50%), 17 acromegaly (38.6%), and 5 patients with Cushing's disease (11.4%). Anthropometric measurements included body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). Health indicators included body fat percentage (BF%), basal metabolic rate (BMR), maximal oxygen uptake (VO2 max), and hand grip strength. Physical activity level (the International Physical Activity Questionnaire [IPAQ]), subjective perception of health, body image (Body Shape Questionnaire), body satisfaction (Stunkard Figure Rating Scale) were used. RESULTS: The mean patient age was 47.2 ± 14.6 years; of which 25 were women (56.8%). Before surgery, 75.0% were overweight or obese, 84.1% had WC with risk of metabolic complications, and 90.0% had WHR with cardiovascular risk. There was a high BF% in 56.4% of cases, low BMR in 65.1%, lower VO2 max in 16.2%, and below-average grip strength in 88.6%. Hypopituitary patients had poorer cardiorespiratory fitness. The IPAQ showed reduction in physical activity, and 79.5% of patients were dissatisfied with their body image. Patients with nonfunctioning adenomas had better perception of their health while those with Cushing's disease had more distorted body image. Postoperatively, patients with acromegaly showed improvement in WHR and physical activity level, and patients with Cushing's disease showed improvement in anthropometric variables. CONCLUSIONS: These findings emphasize the need for continuous monitoring of this population for anthropometric indicators associated with metabolic and cardiovascular comorbidities as well as body satisfaction.

Impact of surgery on pain, disability, and quality of life of patients with degenerative lumbar disease: Brazilian data.

OBJECTIVE: To study the impact of surgery on pain, disability, quality of life, and patient satisfaction in a sample of patients with Degenerative Lumbar Disease (DLD). METHODS: Retrospective analysis of prospectively collected data. Comparison between pre and postoperative (6 - 12 months) ODI and SF-36, plus postoperative Patient Satisfaction Index. RESULTS: From a total of 216 patients included, improvement was observed in average scores of pain (201.2%), disability (39.7%), physical quality of life (42%), and mental quality of life (37.8%). Among these patients, 57.7% reached or surpassed the minimal clinically important difference (MCID) for ODI, 57.7% for the SF-36 pain component, 59.7% for the SF-36 physical component summary, and 50.5% achieved or surpassed the MCID for the SF-36 mental component summary. CONCLUSIONS: Surgery produced a significantly positive impact on pain, disability, and quality of life of patients. Overall, 82.5% of the patients were satisfied.

Physiopathological Aspects of Sellar Epidermoid Cyst Determining Endocrine Disturbances: A Case Report

Epidermoid cysts (ECs) of the central nervous system (CNS) constitute benign circumscribed lesions that aremore common in lateral than in midline sites. Epidermoid cysts of the CNS arise more frequently in the cerebellopontine angle, around the pons, near the sella, within the temporal lobe, in the diploe, and in the spinal canal. Most common tumoral lesion of sellar region is pituitary adenoma, and sellar cystic epithelial masses may be difficult to differentiate based only on clinical and imaging findings. Epidermoid cysts are covered by keratinized squamous epithelium and are usually filled with keratin lamellae. The process is, for the most part, maldevelopmental in origin, presumably arising from trapped surface ectodermal elements in association with the developing CNS during the closure of the neural groove or formation of the secondary cerebral vesicles. In the present study, the authors describe a case of sellar epidermoid cyst producing endocrine alterations and visual disturbance in a 35 years woman, and review the physiopathological and diagnostic criteria of this lesion.

Impact of surgery on pain, disability, and quality of life of patients with degenerative lumbar disease: Brazilian data / Impacto da cirurgia na dor, incapacidade e qualidade de vida de portadores de doença degenerativa lombar: dados brasileiros

ABSTRACT Objective: To study the impact of surgery on pain, disability, quality of life, and patient satisfaction in a sample of patients with Degenerative Lumbar Disease (DLD). Methods: Retrospective analysis of prospectively collected data. Comparison between pre and postoperative (6 - 12 months) ODI and SF-36, plus postoperative Patient Satisfaction Index. Results: From a total of 216 patients included, improvement was observed in average scores of pain (201.2%), disability (39.7%), physical quality of life (42%), and mental quality of life (37.8%). Among these patients, 57.7% reached or surpassed the minimal clinically important difference (MCID) for ODI, 57.7% for the SF-36 pain component, 59.7% for the SF-36 physical component summary, and 50.5% achieved or surpassed the MCID for the SF-36 mental component summary. Conclusions: Surgery produced a significantly positive impact on pain, disability, and quality of life of patients. Overall, 82.5% of the patients were satisfied.

RESUMO Objetivo: Descrever o impacto da cirurgia na dor, incapacidade, qualidade de vida e a satisfação global do paciente numa amostra unificada de pacientes portadores de DDL. Métodos: Análise retrospectiva de dados colhidos prospectivamente em pacientes operados no período de janeiro de 2014 a março de 2017, que tivessem avaliação pré-operatória e pelo menos uma avaliação pós-operatória entre 6 e 12 meses com os questionários de ODI, SF-36 e o ISP. Resultados: Um total 216 pacientes preenchia os critérios de inclusão. Houve melhora no escore médio de dor (201,2%), incapacidade (39,7%), qualidade de vida física (42%) e mental (37,8%). Da amostra, 57,7% alcançaram o MCID de dor, 59,7% de ODI, 59,7% 50,5% de PCS e 50,5% de MCS; 82,5% dos pacientes se consideraram "Satisfeitos". Conclusões: O efeito da cirurgia foi amplamente favorável na dor, incapacidade e qualidade de vida dos pacientes portadores de DDL. Estes dados podem servir de guia para aconselhamento pré-operatório quanto às perspectivas de sucesso.

PTTG overexpression in non-functioning pituitary adenomas: Correlation with invasiveness, female gender and younger age.

BACKGROUND: Non-functioning pituitary adenomas (NFPA) are prevalent pituitary neoplasms. Because they do not present with hormonal hypersecretion, there is no marker that indicates regrowth or recurrence, as in other adenomas. OBJECTIVES: Evaluate the immunohistochemical expression of PTTG, CD105 and Ki-67 and their relationships with age, gender, invasiveness, hormonal expression and regrowth or recurrence in the follow-up of NFPA operated and not submitted to radiotherapy. METHODS: Included 56 patients submitted to transsphenoidal surgery. Clinical data were obtained from medical records. The invasion degree was obtained by Hardy's classification. RESULTS: Mean age 55 ±â€¯13.6 years, 62.5% men and 68% invasive. Lesion persistence was present in 62.2% and regrowth in 35.7%. The recurrence-free survival rate was 94.5%, 75.4% and 69.1% (1, 2 and 3 years). No patient presented recurrence. The PTTG was positive in 55.3%, with statistically significant relationship with invasiveness, age and female gender, without relation to regrowth. The microvascular density showed statistically significant relationship with male gender, negative correlation with PTTG (r = -0.434, p = 0.001), and no relation with invasiveness and regrowth. The Ki-67 showed statistically significant relationship with age, tendency towards regrowth (p = 0.054) and, with no relation to invasiveness. CONCLUSIONS: It is suggested that PTTG can be used as a prognostic marker in NFPA.

Uncovering the Neuroprotective Mechanisms of Curcumin on Transthyretin Amyloidosis.

Transthyretin (TTR) amyloidoses (ATTR amyloidosis) are diseases associated with transthyretin (TTR) misfolding, aggregation and extracellular deposition in tissues as amyloid. Clinical manifestations of the disease are variable and include mainly polyneuropathy and/or cardiomyopathy. The reasons why TTR forms aggregates and amyloid are related with amino acid substitutions in the protein due to mutations, or with environmental alterations associated with aging, that make the protein more unstable and prone to aggregation. According to this model, several therapeutic approaches have been proposed for the diseases that range from stabilization of TTR, using chemical chaperones, to clearance of the aggregated protein deposited in tissues in the form of oligomers or small aggregates, by the action of disruptors or by activation of the immune system. Interestingly, different studies revealed that curcumin presents anti-amyloid properties, targeting multiple steps in the ATTR amyloidogenic cascade. The effects of curcumin on ATTR amyloidosis will be reviewed and discussed in the current work in order to contribute to knowledge of the molecular mechanisms involved in TTR amyloidosis and propose more efficient drugs for therapy.

Evaluation of the potential of the Ki67 index to predict tumor evolution in patients with pituitary adenoma.

The aggressive course of a number of pituitary adenomas requires the investigation of potential predictors. This study aimed to investigate the proliferation marker Ki67 as a predictor of postoperative outcome in patients with pituitary adenoma regarding recurrence and regrowth of the tumor, using a Ki67 cut-off value of 3%. This retrospective study included 52 patients with pituitary adenoma who had undergone adenomectomy and had a pituitary image taken at least 1 year after surgery. Patients were divided according to Ki67 expression into high (≥3%) vs. low (<3%) levels of Ki67. The two groups were similar regarding the preoperative tumor invasion grade. The Ki67 index ranged from 0 to 30%; in 23 cases, Ki67 was ≥3%. The two groups were similar regarding tumor recurrence and regrowth: 4 cases (28%) of recurrence in the Ki67<3% group vs. none in the Ki67≥3% group (P=0.26); and 2 cases (13%) of regrowth in the Ki67<3% group vs. 7 cases (43%) in the Ki67≥3% group (P=0.11). A subgroup analysis was performed for nonfunctioning adenomas. Recurrence rates remained similar between groups (Ki67<3% group: 1 case [20%]; Ki67≥3% group: none; P>0.99), whereas regrowth rates were higher in the Ki67≥3% group (6 cases [67%] vs. 2 cases [17%] in the Ki67<3% group; P=0.03). The patient with the highest Ki67 index (30%) developed pituitary carcinoma. The results allow us to suggest the adoption of a stricter control of image monitoring in nonfunctioning adenomas with incomplete resection associated with a Ki67 index ≥3%.

Gene and protein expression of E-cadherin and NCAM markers in non-functioning pituitary adenomas.

Non-functioning pituitary adenomas (NFPA) are classified as benign tumors of slow growth, but 40% of them present local invasion, a characteristic of behavior still unpredictable with the use of current tumor markers. This work aims to evaluate the tissue markers E-cadherin and NCAM, which act on cell adhesion, in tumor tissue samples of NFPA and its relationship with the degree of local invasiveness. Gene expression of E-cadherin (CDH1) and NCAM (NCAM1) was assessed by real-time PCR and tissue expression by immunohistochemistry. Fifty-three patients with macroadenomas were submitted to transsphenoidal surgery, presented grade II invasive adenomas in 16 cases (30.2%), grade III in 7 (13.2%) and grade IV in 30 (56.6%). In the immunohistochemistry, one case was negative for E-cadherin, 7 showed weak immunostaining, 17 moderate and 28 strong, whereas for NCAM, 5 showed negative, 28 weakly, 14 moderate and 6 strong. Regarding gene expression, 43.3% showed expression for CDH1 (mean of 2.12) and 50% for NCAM1 (mean of 1.86). There was no significant correlation between the immunohistochemical expression of the markers, as well as the gene expression, the degree of invasiveness and clinical data. The results suggest that E-cadherin and NCAM markers are not directly related to the invasiveness in NFPA.

Activity of translation regulator eukaryotic elongation factor-2 kinase is increased in Parkinson disease brain and its inhibition reduces alpha synuclein toxicity.

Parkinson disease (PD) is the second most common neurodegenerative disorder and the leading neurodegenerative cause of motor disability. Pathologic accumulation of aggregated alpha synuclein (AS) protein in brain, and imbalance in the nigrostriatal system due to the loss of dopaminergic neurons in the substantia nigra- pars compacta, are hallmark features in PD. AS aggregation and propagation are considered to trigger neurotoxic mechanisms in PD, including mitochondrial deficits and oxidative stress. The eukaryotic elongation factor-2 kinase (eEF2K) mediates critical regulation of dendritic mRNA translation and is a crucial molecule in diverse forms of synaptic plasticity. Here we show that eEF2K activity, assessed by immuonohistochemical detection of eEF2 phosphorylation on serine residue 56, is increased in postmortem PD midbrain and hippocampus. Induction of aggressive, AS-related motor phenotypes in a transgenic PD M83 mouse model also increased brain eEF2K expression and activity. In cultures of dopaminergic N2A cells, overexpression of wild-type human AS or the A53T mutant increased eEF2K activity. eEF2K inhibition prevented the cytotoxicity associated with AS overexpression in N2A cells by improving mitochondrial function and reduced oxidative stress. Furthermore, genetic deletion of the eEF2K ortholog efk-1 in C. elegans attenuated human A53T AS induced defects in behavioural assays reliant on dopaminergic neuron function. These data suggest a role for eEF2K activity in AS toxicity, and support eEF2K inhibition as a potential target in reducing AS-induced oxidative stress in PD.

Cervicothoracic Lordosis Can Influence Outcome After Posterior Cervical Spine Surgery.

BACKGROUND: Previous studies on the correlation between cervical sagittal balance with improvement in quality of life showed significant results only for parameters of the anterior translation of the cervical spine (such as C2-C7 SVA). OBJECTIVE: We test whether a new parameter, cervicothoracic lordosis, can predict clinical success in this type of surgery. METHODS: The focused group involved patients who underwent surgical treatment of cervical degenerative disk disease by the posterior approach, due to myelopathy, radiculopathy or a combination of both. Neurologic deficit was measured before and after surgery with the Nurick Scale, postoperative quality of life, physical and mental components of SF-36 and NDI. Cervicothoracic lordosis and various sagittal balance parameters were also measured. Cervicothoracic lordosis was defined as the angle between: a) the line between the centroid of C2 and the centroid of C7; b) the line between the centroid of C7 and the centroid of T6. Correlations between postoperative quality of life and sagittal parameters were calculated. RESULTS: Twenty-nine patients between 27 and 78 years old were evaluated. Surgery types were simple decompression (laminectomy or laminoforaminotomy) (3 patients), laminoplasty (4 patients) and laminectomy with fusion in 22 patients. Significant correlations were found for C2-C7 SVA and cervicothoracic lordosis. C2-C7 SVA correlated negatively with MCS (r=-0.445, p=0.026) and PCS (r=-0.405, p=0.045). Cervicothoracic lordosis correlated positively with MCS (r=0.554, p= 0.004) and PCS (r=0.462, p=0.020) and negatively with NDI (r=-0.416, p=0.031). CONCLUSION: The parameter cervicothoracic lordosis correlates with improvement of quality life after surgery for cervical degenerative disk disease by the posterior approach.

Polo-like kinase 2 modulates α-synuclein protein levels by regulating its mRNA production.

Variations in the α-synuclein-encoding SNCA gene represent the greatest genetic risk factor for Parkinson's disease (PD), and duplications/triplications of SNCA cause autosomal dominant familial PD. These facts closely link brain levels of α-synuclein with the risk of PD, and make lowering α-synuclein levels a therapeutic strategy for the treatment of PD and related synucleinopathies. In this paper, we corroborate previous findings on the ability of overexpressed Polo-like kinase 2 (PLK-2) to decrease cellular α-synuclein, but demonstrate that the process is independent of PLK-2 phosphorylating S129 in α-synuclein because a similar reduction is achieved with the non-phosphorable S129A mutant α-synuclein. Using a specific PLK-2 inhibitor (compound 37), we demonstrate that endogenous PLK-2 phosphorylates S129 only in some cells, but increases α-synuclein protein levels in all tested cell cultures and brain slices. PLK-2 is found to regulate the transcription of α-synuclein mRNA from both the endogenous mouse SNCA gene and transgenic vectors that only contain the open reading frame. Moreover, we are the first to show that regulation of α-synuclein by PLK-2 is of physiological importance since 10days' inhibition of endogenous PLK-2 in wt C57BL/6 mice increases endogenous α-synuclein protein levels. Our findings collectively demonstrate that PLK-2 regulates α-synuclein levels by a previously undescribed transcription-based mechanism. This mechanism is active in cells and brain tissue, opening up for alternative strategies for modulating α-synuclein levels and thereby for the possibility of modifying disease progression in synucleinopaties.

Pre-clinical evaluation of voltage-gated calcium channel blockers derived from the spider P. nigriventer in glioma progression.

This study investigated the effects of P/Q- and N-type voltage-gated calcium channel (VGCC) blockers derived from P. nigriventer in glioma progression, by means of in vitro and in vivo experiments. Glioma cells M059J, U-138MG and U-251MG were used to evaluate the antiproliferative effects of P/Q- and N-type VGCC inhibitors PhTx3-3 and Phα1ß from P. nigriventer (0.3-100 pM), in comparison to MVIIC and MVIIA from C. magus (0.3-100 pM), respectively. The toxins were also analyzed in a glioma model induced by implantation of GL261 mouse cells. PhTx3-3, Phα1ß and MVIIA displayed significant inhibitory effects on the proliferation and viability of all tested glioma cell lines, and evoked cell death mainly with apoptosis characteristics, as indicated by Annexin V/propidium iodide (PI) positivity. The antiproliferative effects of toxins were confirmed by flow cytometry using Ki67 staining. None of the tested toxins altered the proliferation rates of the N9 non-tumor glial cell line. Noteworthy, the administration of the preferential N-type VGCC inhibitors, Phα1ß (50 pmol/site; i.c.v.), its recombinant form CTK 01512-2 (50 pmol/site; i.c.v. and i.t.), or MVIIA (10 pmol/site; i.c.v.) caused significant reductions of tumor areas in vivo. N-type VGCC inhibition by Phα1ß, CTK 01512-2, and MVIIA led to a marked increase of GFAP-activated astrocytes, and Iba-1-positive microglia, in the peritumoral region, which might explain, at least in part, the inhibitory effects of the toxins in tumor development. This study provides novel evidence on the potential effects of P. nigriventer-derived P/Q-, and mainly, N-type VGCC inhibitors, in glioma progression.