Voxel-based analysis of gray matter relaxation rates shows different correlation patterns for cognitive impairment and physical disability in relapsing-remitting multiple sclerosis.

BACKGROUND: Regional analyses of markers of microstructural gray matter (GM) changes, including relaxation rates, have shown inconsistent correlations with physical and cognitive impairment in MS. OBJECTIVE: To assess voxelwise the correlation of the R1 and R2 relaxation rates with the physical and cognitive impairment in MS. METHODS: GM R1 and R2 relaxation rate maps were obtained in 241 relapsing-remitting MS patients by relaxometric segmentation of MRI studies. Correlations with the Expanded Disability Status Scale (EDSS) and the percentage of impaired cognitive test (Brief Repeatable Battery and Stroop Test, available in 186 patients) were assessed voxelwise, including voxel GM content as nuisance covariate to remove the effect of atrophy on the correlations. RESULTS: Extensive clusters of inverse correlation between EDSS and R2 were detected throughout the brain, while inverse correlations with R1 were mostly limited to perirolandic and supramarginal cortices. Cognitive impairment correlated negatively with R1, and to a lesser extent with R2, in the middle frontal, mesial temporal, midcingulate and medial parieto-occipital cortices. CONCLUSION: In relapsing-remitting MS patients, GM microstructural changes correlate diffusely with physical disability, independent of atrophy, with a preferential role of the sensorimotor cortices. Neuronal damage in the limbic system and dorsolateral prefrontal cortices correlates with cognitive dysfunction.

Correlação entre os índices antropométricos e pressão arterial de adolescentes e adultos jovens em um município do nordeste brasileiro / Correlation between anthropometric indices and blood pressure in adolescents and young adults in a municipality of northeast Brazil

Introdução:A Hipertensão Arterial Sistêmica tem apresentado alta mortalidade em todo o mundo, associada a fatores de risco cardiovascular como o excesso de peso e a obesidade abdominal.Objetivo:Avaliar os índices antropométricos e pressão arterial em adolescentes e adultos jovens do município de Santa Cruz-RN.Método:Trata-se de um estudo quantitativo, do tipo transversal, realizado com 86 indivíduos com idade média de 19,0 ± 0,97 anos. Foram avaliados o Índice deMassa Corporal (IMC), Relação Cintura Estatura (RCE), Relação Cintura Quadril (RCQ), Índice de Conicidade (IC) e Pressão Arterial (PA). Os dados foram analisados no programa SPSS versão 23.0, apresentados em percentual, média e desvio padrão. O teste T deStudentfoi aplicado para avaliar a diferença entre as médias, a correlação entre medidas antropométricas e a pressão arterial pela correlação de Pearson.Resultados:A prevalência maior foi do sexo feminino, 81,4%. A obesidade esteve mais presente nos meninos adolescentes do que nas meninas, 33,3 e 13,9% respectivamente, bem como nos adultos jovens 28,6% em homens e 11,8% em mulheres. A RCE se mostrou mais elevada nas meninas e mulheres adultas (0,46 ± 0,07, 0,50 ± 0,08). Em contrapartida, a RCQ e IC se mostraram maiores nos meninos(0,79 ± 0,06; 1,12 ± 0,74) e nos homens adultos(0,82 ± 0,09; 1,15 ± 0,12) respectivamente. Em ambos os grupos houve correlação positiva moderada entre o IMC e a RCE com a PA (p<0,05).Conclusão:Os índices antropométricosapresentaram correlação positiva com a elevação da pressão arterial, destacando-se o IMC e a RCE nos adolescentes e adultos jovens (AU).

Introduction:Systemic arterial hypertension has presented high mortality worldwide, associated with cardiovascular risk factors such as overweight and abdominal obesity.Objective:To evaluate the anthropometric indexes and blood pressure in adolescents and young adults in the municipality of Santa Cruz-RN.Methods:This is a cross-sectional quantitative study of 86 individuals with a mean age of 19.0 ± 0.97 years. Body mass index (BMI), Waist Stature Ratio (WSR), Waist Hip Ratio (WHR), Conicity Index (CI) and Blood Pressure (BP) were evaluated. Data were analyzed using SPSS version 23.0, presented in percentage, mean and standard deviation. The T test was applied to evaluate the difference between the means, the correlation between anthropometric measures and blood pressure by the Pearson correlation.Results:The highest prevalence was female, 81.4%. Obesity was more present in adolescent boys than in girls, 33.3 and 13.9% respectively, as well as in young adults, 28.6% in men and 11.8% in women. The WSR was higher in girls and adult women (0.46 ± 0.07, 0.50 ± 0.08). On the other hand, WHR and CI were higher in boys(0.79 ± 0.06, 1.12 ± 0.74)and in adult males (0.82 ± 0.09, 1.15 ± 0.12) respectively. In both groups there was a moderate positive correlation between BMI and WSR with BP (p <0.05).Conclusion:The anthropometric indices showed a positive correlation with the elevation of blood pressure, especially BMI, WSR in adolescents and young adults (AU).

Working memory and phonological awareness in children with Rolandic Epilepsy / Memoria de trabajo y consciencia fonológica en niños con Epilepsia Rolándica

This study investigated how the difficulties in language in children with Rolandic Epilepsy (RE) could be related to alterations in their development of phonological awareness and/or working memory. We evaluated fourty-two children aged 6 to 13 years old. From these, twenty-one children were diagnosed with RE and formed the experimental group; and twenty-one children without RE, paired with the experimental group by sex, age, education and socioeconomic status, formed the control group. The results showed significant differences in the performances of children with RE and healthy children in the tests that evaluated working memory and phonological awareness. Also, positive and high significant correlations were found between working memory and phonological awareness in the RE clinical subgroup. Generally, the results suggest that compromises in both cognitive functions might be associated to loss of language capabilities in children with RE, and also point that the development of working memory and phonological awareness are interconnected.

En este estudio se investigó cómo las dificultades en el lenguaje en niños con epilepsia Rolandica (ER) podrían estar relacionadas con alteraciones en su desarrollo de la conciencia fonológica y/o memoria de trabajo. Se evaluaron 42 niños de 6 a 13 años de edad. De éstos, 21 niños fueron diagnosticados con ER y formaron el grupo experimental; y 21 niños sin RE, emparejados con el grupo experimental por sexo, edad, nivel educativo y socioeconómico, que formaron el grupo de control. Los resultados mostraron diferencias significativas en los resultados de los niños con ER y niños sanos en las pruebas que evaluaron la memoria de trabajo y la conciencia fonológica. Además, se encontraron correlaciones positivas y altas entre la memoria de trabajo y la conciencia fonológica en el subgrupo clínico RE. En general, los resultados sugieren que los compromisos en ambas funciones cognitivas pueden estar asociados a la pérdida de capacidades del lenguaje en los niños con RE, y también señalan que el desarrollo de la memoria de trabajo y la conciencia fonológica están interconectados.

Role of D-Limonene in autophagy induced by bergamot essential oil in SH-SY5Y neuroblastoma cells.

Bergamot (Citrus bergamia, Risso et Poiteau) essential oil (BEO) is a well characterized, widely used plant extract. BEO exerts anxiolytic, analgesic and neuroprotective activities in rodents through mechanisms that are only partly known and need to be further investigated. To gain more insight into the biological effects of this essential oil, we tested the ability of BEO (0.005-0.03%) to modulate autophagic pathways in human SH-SY5Y neuroblastoma cells. BEO-treated cells show increased LC3II levels and appearance of dot-like formations of endogenous LC3 protein that colocalize with the lysosome marker LAMP-1. Autophagic flux assay using bafilomycin A1 and degradation of the specific autophagy substrate p62 confirmed that the observed increase of LC3II levels in BEO-exposed cells is due to autophagy induction rather than to a decreased autophagosomal turnover. Induction of autophagy is an early and not cell-line specific response to BEO. Beside basal autophagy, BEO also enhanced autophagy triggered by serum starvation and rapamycin indicating that the underlying mechanism is mTOR independent. Accordingly, BEO did not affect the phosphorylation of ULK1 (Ser757) and p70(S6K) (Thr389), two downstream targets of mTOR. Furthermore, induction of autophagy by BEO is beclin-1 independent, occurs in a concentration-dependent manner and is unrelated to the ability of BEO to induce cell death. In order to identify the active constituents responsible for these effects, the two most abundant monoterpenes found in the essential oil, d-limonene (125-750 µM) and linalyl acetate (62.5-375 µM), were individually tested at concentrations comparable to those found in 0.005-0.03% BEO. The same features of stimulated autophagy elicited by BEO were reproduced by D-limonene, which rapidly increases LC3II and reduces p62 levels in a concentration-dependent manner. Linalyl acetate was ineffective in replicating BEO effects; however, it greatly enhanced LC3 lipidation triggered by D-limonene.

Implication of limonene and linalyl acetate in cytotoxicity induced by bergamot essential oil in human neuroblastoma cells.

Bergamot (Citrus bergamia, Risso et Poiteau) essential oil (BEO) is a widely used plant extract showing anxiolytic, analgesic and neuroprotective effects in rodents; also, BEO activates multiple death pathways in cancer cells. Despite detailed knowledge of its chemical composition, the constituent/s responsible for these pharmacological activities remain largely unknown. Aim of the present study was to identify the components of BEO implicated in cell death. To this end, limonene, linalyl acetate, linalool, γ-terpinene, ß-pinene and bergapten were individually tested in human SH-SY5Y neuroblastoma cultures at concentrations comparable with those found in cytotoxic dilutions of BEO. None of the tested compounds elicited cell death. However, significant cytotoxicity was observed when cells were cotreated with limonene and linalyl acetate whereas no other associations were effective. Only cotreatment, but not the single exposure to limonene and linalyl acetate, replicated distinctive morphological and biochemical changes induced by BEO, including caspase-3 activation, PARP cleavage, DNA fragmentation, cell shrinkage, cytoskeletal alterations, together with necrotic and apoptotic cell death. Collectively, our findings suggest a major role for a combined action of these monoterpenes in cancer cell death induced by BEO.

Toxic profile of bergamot essential oil on survival and proliferation of SH-SY5Y neuroblastoma cells.

Cosmetic, pharmaceutical, food and confectionary industries make increasing use of plant extracts in their products. Despite the widespread use of products containing plant extracts, the mechanisms of their effects are not fully characterized. Bergamot essential oil (BEO; Citrus bergamia, Risso) is a well-known plant extract used in aromatherapy and it has analgesic, anxiolytic and neuroprotective effects in rodents. To elicit neuroprotection, BEO recruits Akt prosurvival pathways. However, Akt stimulates cell proliferation, which may also pose risks for health in case of prolonged use. To study the potential effects of BEO on survival and proliferation of dividing cells, we selected human SH-SY5Y neuroblastoma cells. BEO triggered concentration-dependent mitochondrial dysfunction, cytoskeletal reorganization, cell shrinkage, DNA fragmentation and both caspase-dependent and independent cell death. Analysis of cleavage products of poly-(ADP-ribose) polymerase (PARP) revealed caspase-3 activation, but also activation of additional protease families. As result of increased proteolytic activity, Akt protein levels decreased in BEO-treated cells. Our data show that BEO can be lethal for dividing cells by activating multiple pathways. While this may reduce the risk of unwanted cell proliferation after prolonged use, it does suggest a cautionary approach to the use of inappropriate dilutions of the oil that may cause cell death.