CRISPR-Cas and its wide-ranging applications: from human genome editing to environmental implications, technical limitations, hazards and bioethical issues

The CRISPR-Cas system is a powerful tool for in vivo editing the genome of most organisms, including man. During the years this technique has been applied in several fields, such as agriculture for crop upgrade and breeding including the creation of allergy-free foods, for eradicating pests, for the improvement of animal breeds, in the industry of bio-fuels and it can even be used as a basis for a cell-based recording apparatus. Possible applications in human health include the making of new medicines through the creation of genetically modified organisms, the treatment of viral infections, the control of pathogens, applications in clinical diagnostics and the cure of human genetic diseases, either caused by somatic (e.g., cancer) or inherited (mendelian disorders) mutations. One of the most divisive, possible uses of this system is the modification of human embryos, for the purpose of preventing or curing a human being before birth. However, the technology in this field is evolving faster than regulations and several concerns are raised by its enormous yet controversial potential. In this scenario, appropriate laws need to be issued and ethical guidelines must be developed, in order to properly assess advantages as well as risks of this approach. In this review, we summarize the potential of these genome editing techniques and their applications in human embryo treatment. We will analyze CRISPR-Cas limitations and the possible genome damage caused in the treated embryo. Finally, we will discuss how all this impacts the law, ethics and common sense

Phylogenetic and Metabolic Tracking of Gut Microbiota during Perinatal Development

The colonization and development of gut microbiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS) and 6 vaginally (V) delivered neonates (DNs), were included in this study and 121 meconium/faecal samples were collected at days 1 through 30 following birth. Operational taxonomic units (OTUs) were assessed in 69 stool samples by phylogenetic microarray HITChip and inter- and intra-individual distributions were established by inter-OTUs correlation matrices and OTUs co-occurrence or co-exclusion networks. H-1-NMR metabolites were determined in 70 stool samples, PCA analysis was performed on 55 CS DNs samples, and metabolome/OTUs co-correlations were assessed in 45 CS samples, providing an integrated map of the early microbiota OTUs-metabolome. A microbiota "core" of OTUs was identified that was independent of delivery mode and lactation stage, suggesting highly specialized communities that act as seminal colonizers of microbial networks. Correlations among OTUs, metabolites, and OTUs-metabolites revealed metabolic profiles associated with early microbial ecological dynamics, maturation of milk components, and host physiology.Peer reviewe

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Capacity to consent to research in older adults with normal cognitive functioning, mild and major neurocognitive disorder: an Italian study

Background: A specific evaluation of the capacity to consent to research in older adults with cognitive decline is often not included routinely in research practice. However, there is a need to evaluate this competence adopting brief standardized instruments to guarantee their ethical rights. The present study evaluated in older adults with normal cognitive functioning, and major and mild neurocognitive disorders whether the Mini-Mental State Examination (MMSE) and a brief battery of neuropsychological tests are sensitive and specific to discriminate subjects able to provide consent to research. Methods: 54 participants with Major Neurocognitive Disorder (MajorNCD), 22 with Mild Neurocognitive Disorder (MildNCD), and 37 Normal Cognitive Functioning individuals (NCF). The capacity to provide consent was assessed using the MacArthur Competence Assessment Tool for Clinical Research. Cognitive functioning was assessed using the MMSE, Verbal Fluency Tests, Trail Making Test (TMT-A), Immediate and Delayed Recall Test. Results: In the MildNCD and NCF groups, the aggregate score of neuropsychological tests showed high sensitivity and specificity in classifying subjects able to provide consent to research. In the MajorNCD group, MMSE, Recall test, and TMT-A performed better than the aggregate score in classifying subjects as able of consenting to the hypothetical research. Conclusion: The choice of the best tool to assess the ability to provide consent to research may depend on the degree of cognitive impairment. MMSE is a good tool for subjects with MajorNCD. A more comprehensive battery of neuropsychological tests would represent a better tool in NCF and MildNCD individuals

The effect of strategic memory training in older adults: who benefits most?

BACKGROUND: Previous research has suggested that there is a degree of variability among older adults' response to memory training, such that some individuals benefit more than others. The aim of the present study was to identify the profile of older adults who were likely to benefit most from a strategic memory training program that has previously proved to be effective in improving memory in healthy older adults. METHOD: In total, 44 older adults (60-83 years) participated in a strategic memory training. We examined memory training benefits by measuring changes in memory practiced (word list learning) and non-practiced tasks (grocery list and associative learning). In addition, a battery of cognitive measures was administered in order to assess crystallized and fluid abilities, short-term memory, working memory, and processing speed. RESULTS: Results confirmed the efficacy of the training in improving performance in both practiced and non-practiced memory tasks. For the practiced memory tasks, results showed that memory baseline performance and crystallized ability predicted training gains. For the non-practiced memory tasks, analyses showed that memory baseline performance was a significant predictor of gain in the grocery list learning task. For the associative learning task, the significant predictors were memory baseline performance, processing speed, and marginally the age. CONCLUSIONS: Our results indicate that older adults with a higher baseline memory capacity and with more efficient cognitive resources were those who tended to benefit most from the training. The present study provides new avenues in designing personalized intervention according to the older adults' cognitive profil

Docosahexaenoic acid supplementation during pregnancy: A potential tool to prevent membrane rupture and preterm labor

none8noPolyunsaturated fatty acids (PUFAs) are required to maintain the fluidity, permeability and integrity of cell membranes. Maternal dietary supplementation with ω-3 PUFAs during pregnancy has beneficial effects, including increased gestational length and reduced risk of pregnancy complications. Significant amounts of ω-3 docosahexaenoic acid (DHA) are transferred from maternal to fetal blood, hence ensuring high levels of DHA in the placenta and fetal bloodstream and tissues. Fetal DHA demand increases exponentially with gestational age, especially in the third trimester, due to fetal development. According to the World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO), a daily intake of DHA is recommended during pregnancy. Omega-3 PUFAs are involved in several anti-inflammatory, pro-resolving and anti-oxidative pathways. Several placental disorders, such as intrauterine growth restriction, premature rupture of membranes (PROM) and preterm-PROM (pPROM), are associated with placental inflammation and oxidative stress. This pilot study reports on a preliminary evaluation of the significance of the daily DHA administration on PROM and pPROM events in healthy pregnant women. Further extensive clinical trials will be necessary to fully elucidate the correlation between DHA administration during pregnancy and PROM/pPROM occurrence, which is related in turn to gestational duration and overall fetal health. © 2014 by the authors; licensee MDPI, Basel, Switzerland.mixedPietrantoni, Emanuela; Del Chierico, Federica; Rigon, Giuliano; Vernocchi, Pamela; Salvatori, Guglielmo; Manco, Melania; Signore, Fabrizio; Putignani, LorenzaPietrantoni, Emanuela; Del Chierico, Federica; Rigon, Giuliano; Vernocchi, Pamela; Salvatori, Guglielmo; Manco, Melania; Signore, Fabrizio; Putignani, Lorenz