The present study examined the level of generation of reactive oxygen species (ROS) and roles of inactivation of the phosphatase PTEN and the PI3K/Akt signaling pathway in response to an increase in intramural pressure-induced myogenic cerebral arterial constriction. Step increases in intraluminal pressure of cannulated cerebral arteries induced myogenic constriction and concomitant formation of superoxide (O2 .−) and its dismutation product hydrogen peroxide (H2O2) as determined by fluorescent HPLC analysis, microscopic analysis of intensity of dihydroethidium fluorescence and attenuation of pressure-induced myogenic constriction by pretreatment with the ROS scavenger 4,hydroxyl-2,2,6,6-tetramethylpiperidine1-oxyl (tempol) or Mito-tempol or MitoQ in the presence or absence of PEG-catalase. An increase in intraluminal pressure induced oxidation of PTEN and activation of Akt. Pharmacological inhibition of endogenous PTEN activity potentiated pressure-dependent myogenic constriction and caused a reduction in NPo of a 238 pS arterial KCa channel current and an increase in [Ca2+]i level in freshly isolated cerebral arterial muscle cells (CAMCs), responses that were attenuated by Inhibition of the PI3K/Akt pathway. These findings demonstrate an increase in intraluminal pressure induced increase in ROS production triggered redox-sensitive signaling mechanism emanating from the cross-talk between oxidative inactivation of PTEN and activation of the PI3K/Akt signaling pathway that involves in the regulation of pressure-dependent myogenic cerebral arterial constriction.

Background: Parent-clinician shared decision making is the recommended model for the care of premature infants; thus, clinicians provide prenatal prematurity counseling to parents in the event of a mother's hospitalization for premature birth. However, parental understanding of medical jargon commonly used during prematurity counseling is unknown. Methods: Within an overall research agenda to develop and test an educational aid for prenatal prematurity education, we designed the Parental Knowledge of Premature Birth questionnaire. To evaluate parental comprehension of the medical jargon contained within the questionnaire, we conducted cognitive interviews, a formal method for evaluating comprehension and response to questionnaire items. Parents were recruited from a Level IV Neonatal Intensive Care Unit; purposeful recruitment ensured diversity with respect to gender, race, literacy level, and child's gestational age. Data collection and analysis followed standard qualitative methods for cognitive interviewing. We report on the insights gained from these cognitive interviews regarding parental understanding of crucial medical jargon commonly used during prenatal prematurity counseling. Results: Participants included 10 women and 6 men who ranged in age from 23 to 38 years and represented Black/African-American (38%), Asian (6%), and white (56%) backgrounds. Five participants (31%) had less than a high school education or reading level below 9th grade (Wide Range Achievement Test version 4 reading subtest). In the first round of interviews, parents of all education and literacy levels had difficulty with medical jargon commonly used in prematurity counseling. Terms that parents found difficult to understand included "gestational age", "mild or no developmental problems", and "neonatologist". Modified terms tested in a second round of interviews showed improved comprehension. Conclusion: Cognitive interviews provided empirical testing of parental understanding of crucial medical jargon and highlighted that language commonly used during prenatal prematurity counseling is not understood by many parents. For parents to participate in shared decision making, plain language should be used to maximize their understanding of medical information.

Astrocytes secrete vasodilator and vasoconstrictor factors via end feet processes, altering blood flow to meet neuronal metabolic demand. Compared to what is known about the ability of astrocytes to release factors that dilate local cerebral vasculature, very little is known regarding the source and identity of astrocyte derived constricting factors. The present study investigated if astrocytes express CYP 4A ω-hydroxylase and metabolize arachidonic acid (AA) to 20-hydroxyeicotetraenoic acid (20-HETE) that regulates KCa channel activity in astrocytes and cerebral arterial myocyte contractility. Here we report that cultured astrocytes express CYP 4A2/3 ω-hydroxylase mRNA and CYP 4A protein and produce 20-HETE and the CYP epoxygenase metabolites epoxyeicosatrienoic acids (EETs) when incubated with AA. The production of 20-HETE and EETs was enhanced following stimulation of metabotropic glutamate receptors (mGluR) on the astrocytes. Exogenous application of 20-HETE attenuated, whereas inhibition of 20-HETE production with HET-0016 increased the open state probabilities (NPo) of 71 pS and 161 pS KCa single-channel currents recorded from astrocytes. Exposure of isolated cerebral arterial myocytes to conditioned media from cultured astrocytes caused shortening of the length of freshly isolated cerebral arterial myocytes that was not evident following inhibition of astrocyte 20-HETE synthesis and action. These findings suggest that astrocytes not only release vasodilator EETs in response to mGluR stimulation but also synthetize and release the cerebral arterial myocyte constrictor 20-HETE that also functions as an endogenous inhibitor of the activity of two types of KCa channel currents found in astrocytes.

No abstract

Background: Parents at risk for preterm birth frequently receive prematurity education when the mother is hospitalized for premature labor. Parental ability to learn and consider the information is limited due to the stress of the hospitalization. A promising approach is dissemination of information to at-risk parents before the birth hospitalization.Purpose: This manuscript describes formative research used to develop smartphone-based prematurity education app for parents at-risk for preterm birth.Methods: Stakeholders were parents with a prior preterm birth. Using stakeholder meeting transcripts, constant comparative analysis was used to reflect upon the parental voice. Results:The parents named the app, Preemie Prep for Parents (P3). Parent perspectives revealed desire for information in the following five categories. (1) Power in knowledge and control: parents want autonomy when learning information that may influence medical decision-making.(2) Content and framing of information: they desire information from a trusted resource that helps promote prenatal health and provides neonatal intensive care information. (3) Displaying content: parents want personalization, push-notifications, pictures displaying fetal development and easy to understand statistics. (4) Providing information without causing harm: they desire non-value laden information and they do not support "gamifying" the app to enhance utilization. (5) Decisionmaking: parents want information that would benefit their decision-making without assuming that parents have a certain outlook on life or particular values.Implications for Practice: These findings support the need for the P3 App to aid in decisionmaking when parents experience preterm birth.