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Browsing by Issue Date, starting with "2017-02-21"

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  • To CRISPR or not to CRISPR
    Publication . Duarte, A.J.; Amaral, Olga; Bragança, José
    The CRISPR/Cas9 genome editing system is a most promising tool but the application of this method to Lysosomal Storage diseases (LSDs) still needs to be explored. In LSDs, enzyme replacement therapy (ERT, regular supplementation of the defective enzyme) is the most common treatment to clear the accumulated substrates in patient cells and it is effective in a few diseases. However, there are many limits to its cost-effective application. The lack of good in vitro models hinders R&D and the understanding of the human pathophysiologic mechanisms. Using CRISPR/Cas9-mediated gene editing, to either make a model and test therapeutic approaches or to correct a causal mutation and examine the potential effects on the cellular environment will likely provide important information for functional studies. Induced pluripotent stem cells (iPSCs) from patients, with several genetic diseases, including LSDs, have been successfully established. Patient-derived iPSCs present the advantage of having the patient’s genetic background with all corresponding influences on the disease’s mechanism. Therefore, these iPSCs, differentiated into the disease specific target cell types, offer an ideal model for studying pathogenic mechanisms and therapies. Gene editing using CRISPR/Cas9 in combination with iPSCs seems like a perfect match. Currently, we are generating iPSCs from human fibroblasts and intend to proceed with gene editing. However, despite the apparently simple approach, there are still problems with CRISPR. Besides the ethical problems, there are practical problems such as diminishing off-targeting. Therefore, the question is, how feasible will CRISPR/Cas9 be? No doubt it is promising and valuable but will it be safe enough?
    2017-02-21Conference object Restricted access Show more
  • Obstructive Sleep Apnea: Epidemiology and Portuguese patients profile
    Publication . Rodrigues, Ana Paula; Pinto, Paula; Nunes, Baltazar; Bárbara, Cristina
    Introduction: Obstructive Sleep Apnea (OSA) is characterized by recurrent episodes of apnea and hypopnea, secondary to collapse of the upper airways during sleep. OSA is frequently associated to cardiovascular complications. In Portugal, its magnitude is unknown. Methods: In 2014 a cross-sectional study was performed using the Portuguese General Practi- tioner (GP) Sentinel Network (Rede Médicos Sentinela). Participants GP reported all OSA cases diagnosed and registered in their lists of users on the 31 December 2013. Frequency of OSA has been estimated by sex and age. OSA patients were also characterized by method of diagnosis, treatment, and underlying conditions. Association between risk factors and severe OSA (odds ratio) was calculated using a logistic regression model adjusting confounding. Results: Prevalence of OSA on the population aged 25 years or more was 0.89% (95 CI: 0.80-1.00%); it was higher in males 1.47% (95 CI: 1.30-1.67%) and in those aged between 65 and 74 (2.35%). Most had severe OSA (48.4%). Hypertension (75.9%), obesity (74.2%) and diabetes mellitus (34.1%) were the most frequent comorbidities. Being a male (OR: 2.6; 95 CI: 1.2-5.8) and having obesity (OR: 4.0; 95 CI: 1.8-8.6) were associated with an increased risk of severe OSA. Conclusion: Found frequency of OSA was lower than other countries estimates, which may be explained by differences on case definition but can also suggest underdiagnosis of this condition as reported by other authors.
    2017-02-21Journal article Open access Show more