Alignment of druglike compounds in lipid bilayers analyzed by solid-state (19)F-NMR and molecular dynamics, based on dipolar couplings of adjacent CF3 groups.

Solid-state (19)F-NMR spectroscopy is frequently used to analyze the structure and dynamics of lipophilic drugs and peptides embedded in biomembranes. The homonuclear dipolar couplings of trifluoromethyl (CF3) labels can provide valuable parameters such as orientational constraints and/or distances. To characterize the complex dipolar patterns of multiple (19)F spin interactions, three different model compounds carrying two CF3 groups in meta-position on a phenyl ring were incorporated in macroscopically aligned DMPC bilayers. The dipolar patterns obtained with the CPMG (Carr-Purcell-Meiboom-Gill) multipulse sequence were analyzed to yield simultaneously the intra-CF3 and intergroup dipolar coupling values. The fluorine-fluorine distances were predicted by a density functional calculation, and the alignment of the labeled molecular segment could be determined from these distances and the dipolar coupling values. The different compounds were found to align in the lipid bilayer according to their amphiphilic properties, though with a weak anisotropic preference that is typical of solutes in liquid crystals. The residual dipolar couplings were used to calculate Saupe order parameters. For the least complex molecule, (CF3)2-BA, an orientational probability function for the solute in the lipid matrix could be derived. The overall description of how (CF3)2-BA is embedded in the bilayer was independently assessed by molecular dynamics simulations, and compared in structural and dynamical terms with the results of the NMR experiments.

2H-NMR study and molecular dynamics simulation of the location, alignment, and mobility of pyrene in POPC bilayers.

The alignment of pyrene in a 1-palmitoyl-2-oleoyl-phosphatidylcholine bilayer was investigated using two different approaches, namely solid-state (2)H-NMR spectroscopy and molecular dynamics (MD) simulations. Quadrupolar splittings from (2)H-NMR spectra of deuterated pyrene-d(10) in an oriented lipid bilayer give information about the orientation of C-D bonds with respect to the membrane normal. From MD simulations, geometric information is accessible via trajectories. By defining molecular and bond order parameters, the data from MD trajectories and NMR spectra can be compared straightforwardly. To ensure that the results from both methods are comparable, parameters of the experimental and the simulation setup were chosen to be as similar as possible. From simulations, we saw that pyrene prefers a position inside the lipid membrane near the headgroups and has no tendency to diffuse from one monolayer of the membrane to the other. The results from simulation and NMR show that the normal of the molecular plane is aligned nearly perpendicular to the bilayer normal. The long axis of pyrene lies preferentially parallel to the bilayer normal within a range of +/-30 degrees . The results from the two different methods are remarkably consistent. The good agreement can be explained by the fact that the different kind of motions of a pyrene molecule are already averaged within a few nanoseconds, which is the timescale covered by the MD simulation.

Behavioral and social development of children born extremely premature: 5-year follow-up.

A cohort of extremely prematurely born children and matched term controls was assessed at 5 years of age. The parents completed a questionnaire on their behavioral and social development. The purpose was to illuminate whether the children's general intellectual ability and parental sensitivity were associated with behavioral and social development. The index children exhibited more hyperactive behavior and had poorer social skills than the controls. Lower Full Scale IQ (FSIQ) was associated with outward reacting and hyperactive behavior and poorer social skills. Sensitive parenting was associated with less outward reacting and less hyperactive behavior. When controlling for differences in FSIQ and parental sensitivity, the index children persisted to have an increased risk of exhibiting hyperactive behavior but not poorer social skills. The index children with normal intellectual development, however, did not exhibit more behavioral problems or poorer social skills than the control children did.

Assessment of parental sensitivity towards pre-school children born with very low birth weight.

The article introduces the Parental Sensitivity Assessment Scale (PSAS) and examines the influence of the PSAS score and other factors on the general cognitive level in pre-school children born with very low birth weight (VLBW). McCarthy general cognitive index (GCI) was obtained for 102 VLBW and 92 normal birth weight (NBW) control children in Denmark in the mid-1980s. The mean ages of the two groups were 52.4 vs. 53.1 months. Parental sensitivity was assessed using PSAS. There was no significant difference in the mean PSAS score between the two birth weight groups (p > 0.3). Birth weight group (p < 0.001) and mother's schooling (p= 0.026) significantly correlated with GCI in the children. The PSAS score was highly significantly correlated to the variance of the GCI (p < 0.001), which was not explained by VLBW and mother's schooling. We found no interactional effect between parental sensitivity and birth weight group (p > 0.5) - the prematurely born children were not more affected by low parental sensitivity than were the control children.

Intelligence in preterm children at four years of age as a predictor of school function: a longitudinal controlled study.

The aim of the study was to examine whether school performance was reduced in children with very-low birthweight beyond what could be explained by the deficit in intelligence-score at 4 years of age. Participants (n=333) examined at 4 years of age included three subgroups on the basis of birthweight: very-low birthweight (VLBW < 1501 g; n=102), low birthweight (LBW 1500-2300 g; n=139), and normal birthweight (NBW > or = 2500 g; n=92). The general cognitive index index (CGI) from the McCarthy Scales of Children's Abilities was used as an intelligence measurement at this assessment. At 18 to 20 years of age a telephone interview concerning school performance was conducted. Two hundred and fifty-seven participants (53% male, 47% female) entered the analysis. A model with School Performance score after the last year of compulsory school as the outcome variable, and McCarthy GCI and birthweight group as predicting variables, was used in linear regression analyses. Twenty-four per cent of the variance was explained. Birthweight had no influence in this model. In conclusion, the study did not find that birthweight influenced school performance beyond that represented by the McCarthy GCI found at age 4 years.