Improving cognitive development of low-birth-weight premature infants with the COPE program: a pilot study of the benefit of early NICU intervention with mothers.

The purpose of this pilot study was to evaluate the effectiveness of a parent-focused intervention program (COPE) on infant cognitive development and maternal coping. A randomized clinical trial was conducted with 42 mothers of low-birth-weight (LBW) premature infants hospitalized in a neonatal intensive care unit (NICU), with follow-up at 3 months' and 6 months' corrected ages. COPE mothers received the four-phase educational-behavioral program that began 2-4 days postbirth and continued through 1 week following discharge from the NICU. Comparison mothers received audiotaped information during the same four time frames. Results indicated that COPE infants had significantly higher mental development scores at a 3 months' corrected age (M = 100.3) than did the comparison infants (M = 93.9), and this difference widened at 6 months' corrected age, with COPE infants scoring 14 points higher. COPE mothers were significantly less stressed by the NICU sights and sounds and had significantly stronger beliefs about what behaviors and characteristics to expect from their premature infants. Findings from this study support the need for further testing of early NICU interventions with parents to determine their effectiveness on parental coping and infant developmental outcomes.     

The assessment of body image investment: an extensive revision of the appearance schemas inventory

OBJECTIVE: The Appearance Schemas Inventory (ASI) is a 14-item instrument that assesses body image investment in relation to certain beliefs or assumptions about the importance, meaning, and influence of appearance in one's life. Despite empirical support of the ASI, critical examination evinces several limitations of this assessment. These problems entail the inclusion of explicitly self-evaluative items and social stereotypes, few behavioral items, and a repeated failure to find expected gender differences on the ASI. METHOD: We initially constructed a 45-item measure (40 new items plus 5 original items) and administered it, along with the original ASI and other validational assessments, to 603 college students (468 women and 135 men). RESULTS: The end result was a 20-item revision of the inventory (ASI-R), which included two factors: Self-Evaluative Salience and Motivational Salience. For both genders, the composite ASI-R and its two factors had high internal consistency and were significantly convergent with other pertinent measures of body image and psychosocial functioning. The ASI-R and its two subscales showed significant gender differences, whereas the original ASI did not. We also examined racial differences on the ASI-R, its correlations with body mass, and its unique contribution to the prediction of disturbed eating attitudes. DISCUSSION: We offer this measure as an improved, psychometrically sound replacement for the ASI.     

Increased plasma homocysteine and S-adenosylhomocysteine and decreased methionine is associated with altered phosphatidylcholine and phosphatidylethanolamine in cystic fibrosis

OBJECTIVE: We used a novel approach based on the intersection of phospholipid and methionine metabolism at the S-adenosylmethionine (SAM)-dependent methylation of phosphatidylethanolamine (PE) to study potential alterations in phospholipid metabolism in children with cystic fibrosis (CF). Methyl groups from methionine via SAM are used for sequential methylation of PE to form phosphatidylcholine (PC) with the generation of S-adenosylhomocysteine (SAH) and homocysteine. STUDY DESIGN: Plasma phospholipids and methionine metabolites and plasma and red blood cell phospholipid fatty acids were determined in 53 children with CF and 18 control children. RESULTS: Plasma methionine and the PC/PE ratio was lower and homocysteine, SAH, and PE were higher in children with CF than in control children (P<.001). Plasma methionine was inversely (P<.05) and SAH and homocysteine were positively (P<.001) correlated with the plasma PE. Docosahexaenoic acid (22:6n-3) was significantly lower in plasma phospholipids and triglycerides and in red blood cell PC and PE of children with CF than in control children (P<.05). CONCLUSIONS: These studies demonstrate that methionine metabolism is altered and associated with alteration of the plasma PC/PE ratio in CF. Altered phospholipid and methionine metabolism may contribute to the clinical complications associated with CF.     

Targeting Ras signaling through inhibition of carboxyl methylation: an unexpected property of methotrexate

The antifolate methotrexate is one of the most successful drugs in cancer chemotherapy. Although its efficacy is widely attributed to a decrease in nucleotide biosynthesis (1), methotrexate is known to increase homocysteine (2), a compound associated with an elevated risk of heart disease, Alzheimer's disease (3), and neural tube defects (4). A potential mechanism for the detrimental effects of homocysteine is cellular hypomethylation from an increase in S-adenosylhomocysteine (5), an inhibitor of methyltransferases including isoprenylcysteine carboxyl methyltransferase (Icmt). Among the substrates of Icmt is the monomeric G protein Ras, a critical component of many signaling pathways that regulate cell growth and differentiation. Because carboxyl methylation of Ras is important for proper plasma membrane localization and function (6), we investigated the role of Icmt in the antiproliferative effect of methotrexate. After methotrexate treatment of DKOB8 cells, Ras methylation is decreased by almost 90%. This hypomethylation is accompanied by a mislocalization of Ras to the cytosol and a 4-fold decrease in the activation of p44 mitogen-activated protein kinase and Akt. Additionally, cells lacking Icmt are highly resistant to methotrexate. Whereas cells expressing wild-type levels of Icmt are inhibited by methotrexate, stable expression of myristoylated H-Ras, which does not require carboxyl methylation for membrane attachment (7), confers resistance to methotrexate. These results suggest that inhibition of Icmt is a critical component of the antiproliferative effect of methotrexate, expanding our understanding of this widely used drug and identifying Icmt as a target for drug discovery.     

Creating avenues for relative empowerment (CARE): a pilot test of an intervention to improve outcomes of hospitalized elders and family caregivers

The purpose of this pilot study was to evaluate the effectiveness of a family caregiver-focused intervention program (CARE) on the outcomes of hospitalized elders and their family caregivers. A randomized clinical trial was conducted with 49 family caregivers of hospitalized elders in a university medical center in upstate New York. Driven by self-regulation and role theories, the two-phase CARE program consisted of: (a). a mutual agreement consisting of family caregiving activities during hospitalization; and (b). audiotaped information regarding emotional responses and possible complications associated with an elderly patient's hospitalization as well as instructions for effectively participating in the elder's hospital care. The comparison program consisted of information about hospital services and policies. CARE elders had fewer incidents of acute confusion reported by family caregivers during hospitalization and fewer depressive symptoms at 2 weeks and 2 months posthospitalization than did the comparison group. CARE family caregivers participated more in the care of their hospitalized elders and had higher scores on role rewards prior to hospital discharge. Findings from this study support the need for further testing of the CARE intervention with family caregivers to determine its effectiveness on outcomes of hospitalized elders and their family caregivers.     

Effects of dietary folate intake and folate binding protein-1 (Folbp1) on urinary speciation of sodium arsenate in mice

In most mammalian species, arsenic biotransformation occurs primarily by biomethylation with dimethylarsinic acid being the predominant metabolite excreted in the urine. Folbp1 (folate binding protein-1) mediated intracellular folate uptake is one route by which cells harvest folate cofactors. In light of the likely relationship between folate biochemistry and arsenic biotransformation, our experiments were designed to test: (1) whether Folbp1 is an important determinant in arsenic biotransformation, by performing urinary arsenic speciation in Folbp1 nullizygous (Folbp1(-/-)) and wildtype control mice, and (2) whether dietary folate deficiency alters arsenic biotransformation in these mice. Compared to normal folate intake, folate deficiency caused lower amounts of arsenic to be excreted in the urine of both the wildtype controls and Folbp1(-/-) mice. Folbp1(-/-) mice excreted more dimethylarsinic acid than wildtype control mice during folate deficiency, but not during normal folate intake. The present data suggest that inadequate folate intake may result in decreased biotransformation and excretion of arsenic, which is likely to increase arsenic exposure and related toxicities.