Browsing by Author "Santos, Cristina"
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- Circulating miR-134 in mesial temporal lobe epilepsy: implications in hippocampal sclerosis development and drug resistancePublication . Guerra Leal, Bárbara; Carvalho, Cláudia; Santos, Cristina; Samões, Raquel; Martins-Ferreira, Ricardo; Teixeira, Catarina; Rodrigues, Diana; Freitas, Joel; Lemos, Carolina; Chorão, Rui; Ramalheira, João; Lopes, João; Martins da Silva, António; Pinho E Costa, Paulo; Chaves, JoãoAim: miR-134 has been widely reported as upregulated in experimental and human studies of Mesial Temporal Lobe Epilepsy the most common drug-resistant epilepsy (DRE). Studies have shown that the use of antagomirs, anti-miR-134, may be a promising therapeutic approach to these epilepsies. However, data on miR-134 in other epileptic syndromes is scarce. In this study, we aimed to quantify serum levels of miR-134 in a cohort of patients with Mesial Temporal Lobe Epilepsy-Hippocampal Sclerosis (MTLE-HS) and with Genetic Generalized Epilepsies (GGE). Additionally, we explored the correlation between miR-134 serum levels and clinical parameters, such as age at onset or febrile seizures antecedents, to evaluate its potential as a biomarker and therapeutic target in epilepsy. Methods: miR-134 levels were evaluated in cell-free serum of 131 patients with epilepsy (75 women, 56 men; age 41.10 ± 13.12 years; 72 with DRE) and 42 healthy individuals (25 women, 17 men; age 42.40 ± 9.80 years). The epilepsy cohort included 77 MTLE-HS patients and 54 GGE patients. Results: Patients with elevated miR-134 circulating levels were at higher risk of drug-resistant epilepsy (OR [95% CI] = 2.246 [1.111–4.539], p = 0.021). Other risk factors included an older age (OR [95% CI] = 1.032 [1.004–1.061], p = 0.025), history of febrile seizures (OR [95% CI] = 2.994 [1.385–6.471], p = 0.005) and higher disease duration (OR [95% CI] = 1.038 [1.011–1.066], p = 0.006). The strongest predictor of DRE was hippocampal sclerosis (OR [95% CI] = 10.338 [4.566–23.404], p < 0.001). Circulating miR-134 levels were significantly higher in MTLE-HS patients compared to controls (p < 0.05) and GGE patients (p < 0.05). However, the clinical utility of miR-134 in discriminating MTLE-HS patients from controls was only moderated (AUC = 0.651 ± 0.051 95% CI 0.551–0.751, p = 0.007). Conclusion: We show that miR-134 circulating levels are associated with DRE, especially in MTLE-HS, a syndrome characterized by severe hippocampal damage, consistent with activity-regulated miR-134 expression. This overexpression likely contributes to disease progression and our results support the potential of targeting miR-134 as a novel therapeutic approach for refractory epilepsy.
- MicroRNAs as potential biomarkers of response to modified Atkins diet in treatment of adults with drug-resistant epilepsy: A proof-of-concept studyPublication . Samões, Raquel; Cavalheiro, Ana; Santos, Cristina; Lopes, Joana; Teixeira, Catarina; Tavares, Maria Manuel; Carvalho, Cláudia; Lemos, Carolina; Costa, Paulo Pinho e; Cavaco, Sara; Chaves, João; Leal, BárbaraBackground: Accurate predictors of response to modified Atkins diet (MAD) are needed. MicroRNAs are potential biomarkers in epilepsy. This study aimed to explore the value of circulating miR-146a, miR-155, miR-22, miR-21 and miR-134 levels in predicting response to MAD. Methods: Patients who completed 3 months of MAD were selected from a prospective cohort of adults with DRE followed in a specialized MAD outpatient clinic. Patients were classified as responders if any reduction in seizure frequency at follow-up, calculated through seizure-calendars). The >50 % seizure reduction cut-off was also explored. Qualitative benefits in seizures and cognition were analysed. Blood samples were collected prior to initiate MAD and microRNAs were quantified by qRT-PCR. Results: Thirty-nine patients were included (56 %males, mean age=33.1±8.5yo, 62 %focal epilepsies, 59 %structural aetiology): 20(51 %) were responders [mean reduction in seizure frequency=54 %(17-100 %); 10 had ≥50 % reduction]; 25(64 %) reported qualitative benefit in seizures and 21(54 %) reported cognitive benefits. At pre-treatment baseline, a panel combining serum levels of all studied microRNAs predicted seizure reduction (AUC=0.839, p<0.0001), qualitative benefit in seizures (AUC=0.683, p=0.048) and in cognition (AUC=0.751, p<0.01) at 3months. miR-146a was the only significant microRNA when evaluated in isolation. There was no statistical correlation in the biomarkers when a ≥50 % seizure reduction was compared to <50 %. Conclusions: A panel combining pre-treatment serum levels of miR-146a, miR-155, miR-134, miR-21 and miR-22 predicted any reduction in seizures with MAD in adults with DRE at 3months. This panel may be a promising biomarker and a useful tool in the selection of patients.
- Preparação das famílias para fazer face a emergências e catástrofes: avaliação após o incêndio de 2017 ocorrido nos concelhos de Pedrógão Grande, Figueiró dos Vinhos e Castanheira de PeraPublication . Neto, Mariana; Pimentel, João; Morais, António; Santos, Cristina; Ferreira, António J.; Ferreira, Pedro L.Os incêndios florestais constituem uma séria ameaça à saúde das populações e ao ambiente. A preparação das famílias para fazer face a desastres e emergências é crucial para a sua proteção e para a resiliência da comunidade. Aproximadamente um ano depois do incêndio florestal de 2017 ocorrido na região portuguesa de Pedrógão Grande, foi realizado um inquérito sobre medidas de preparação, envolvendo uma amostra aleatória e representativa de 330 pessoas da população afetada. Analisaram-se as relações entre as variáveis sociodemográficas e a adoção de medidas básicas de preparação pelas famílias, bem como do índice de preparação, através de odds ratio, estimadas por regressão logística. A taxa de resposta ao inquérito foi de 83%. Alimentos que não requerem refrigeração nem preparação culinária e o abastecimento de água foram as medidas de preparação mais referidas (85% e 63% respetivamente). Aproximadamente 79% dos respondentes referiram dispor de um rádio a pilhas e 47% de uma lanterna a pilhas, mas apenas 35% verificava regularmente a carga das pilhas. A forma preferida para obter informações durante um desastre ou emergência era a televisão (36,4%), o telefone (22%) e o rádio (15%). A análise do índice de preparação revela a existência de pequenas diferenças a nível local e que as mulheres tendem a adotar menos medidas de preparação que os homens. A existência de doenças crónicas está relacionada com a adoção de um maior número de medidas de preparação.