Ceramide: a novel inducer for neural tube defects.

BACKGROUND: Circulating plasma ceramides, a class of bioactive sphingolipids, are elevated in metabolic disorders, including obesity. Infants of women with these disorders are at 2- to 3-fold greater risk for developing a neural tube defect (NTD). This study aimed to test the effects of embryonic exposure to C2-ceramides (C2) during neural tube closure. Preliminary data shows an increase in NTDs in chick embryos after C2 exposure, and addresses potential mechanisms. RESULTS: Cell and embryo models were used to examine redox shifts after ceramide exposure. While undifferentiated P19 cells were resistant to ceramide exposure, neuronally differentiated P19 cells exhibited an oxidizing shift. Consistent with these observations, GSH E h curves revealed a shift to a more oxidized state in C2 treated embryos without increasing apoptosis or changing Pax3 expression, however cell proliferation was lower. Neural tube defects were observed in 45% of chick embryos exposed to C2, compared to 12% in control embryos. CONCLUSIONS: C2 exposure during critical developmental stages increased the frequency of NTDs in the avian model. Increased ROS generation in cell culture, along with the more oxidative GSH E h profiles of C2 exposed cells and embryos, support a model wherein ceramide affects neural tube closure via altered tissue redox environments.

Persistence of patient and family experiences of critical illness.

OBJECTIVE: To investigate: (1) patient and family experiences with healthcare and the intensive care unit (ICU); (2) experiences during their critical illness; (3) communication and decision making during critical illness; (4) feelings about the ICU experience; (5) impact of the critical illness on their lives; and (6) concerns about their future after the ICU. DESIGN: Four semistructured focus group interviews with former ICU patients and family members. SETTINGS: Multicultural community group and local hospitals containing medical/surgical ICUs. PARTICIPANTS: Patients and family who experienced a critical illness within the previous 10 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four separate focus groups each lasting a maximum of 150 min and consisting of a total of 21 participants were held. Focus groups were conducted using a semistructured script including six topics relating to the experience of critical illness that facilitated deduction and the sorting of data by thematic analysis into five predominant themes. The five main themes that emerged from the data were: (1) personalised stories of the critical illness; (2) communication and shared decision making, (3) adjustment to life after critical illness, (4) trust towards clinical team and relevance of cultural beliefs and (5) end-of-life decision making. Across themes, we observed a misalignment between the medical system and patient and family values and priorities. CONCLUSIONS: The experience of critical illness of a diverse group of patients and families can remain vivid for years after ICU discharge. The identified themes reflect the strength of memory of such pivotal experiences and the importance of a narrative around those experiences. Clinicians need to be aware of the lasting effects of critical illness has on patients and families.