Designs for Instruction, Designs for Change: Distributing Knowledge of Evidence-Based Practice

We comment on the target article by Weingardt (this issue), which discusses recent advances in instructional design and technology (IDT) and their implications for dissemination of evidence-based practices. These arguments are extended to the topic of psychological intervention design, and possibilities for new intervention structures are briefly explored. Finally, comments are offered on maintaining a careful balance between technological and social processes in the effort to promote the dissemination of innovative and evidence-based psychological procedures.     

Porphyromonas gingivalis RgpA and Kgp proteinases and adhesins are C terminally processed by the carboxypeptidase CPG70

Porphyromonas gingivalis is a bacterial pathogen that produces the polyproteins RgpA and Kgp, which are proteolytically processed into proteinases and adhesins. We have demonstrated that the RgpA and Kgp proteinases and adhesins are C terminally processed by carboxypeptidase CPG70 by sequencing C-terminal peptides from both the wild type and an isogenic CPG70 mutant, using ion trap mass spectrometry.     

The FREP gene family in the snail Biomphalaria glabrata: additional members,and evidence consistent with alternative splicing and FREP retrosequences. Fibrinogen-related proteins

Fibrinogen-related proteins (FREPs) found in hemolymph of the snail Biomphalara glabrata are hypothesized to be involved in non-self recognition. Among 150 cloned FREP cDNAs examined, we have identified three additional FREP members, FREPs 3.3, 12.1 and 13.1, bringing the total of FREP subfamilies to 13. The new FREPs each encode two immunoglobulin superfamily domains and a fibrinogen domain. Additionally, five truncated cDNAs with >99% nucleotide identity in coding regions to FREPs 3.2, 12.1 or 13.1 were identified. The truncated forms, the first reported for FREPs, lack a partial exon, one complete exon, or two complete exons plus the 3'UTR. Our preferred hypothesis is that all five truncated cDNAs observed arise from alternative splicing of full-length FREP genes. Genomic sequences lacking at least two introns and corresponding to the 3' ends of the cDNAs of FREP12.1 and its two truncated forms were also recovered. Although these could be the source of the truncated cDNAs, they are believed to be retrosequences.     

Phosphoinositide deficiency due to inositol depletion is not a mechanism of lithium action in brain

The "inositol depletion hypothesis" has been widely held to be the explanation for both the effect of lithium on brain function, apropos of its use in mood disorders, and on the impairment of development and induction of embryonic malformations in diverse organisms. The essence of the hypothesis is that a deficiency in cellular myo-inositol (Ins), secondary to lithium inhibition of inositol monophosphatase and/or multiple inositol polyphosphate phosphatase activities with trapping of Ins as inositol phosphates, leads to a depression of phosphatidylinositol (PtdIns) and a secondary impairment in inositide signaling. However, the ability of relatively low micromolar levels of Ins to reduce mammalian PtdIns synthetase activity in vivo has never been adequately tested. We have generated a lethal murine brain Ins deficiency model and measured PtdIns content using a novel MALDI-TOF MS method. Our results show that in the most severe Ins deficiency ever recorded in a mammal, the brain PtdIns levels do not decrease. We conclude that PtdIns deficiency due to "inositol depletion" is not a mechanism of lithium action in brain, and that Ins plays another unidentified role in the mammalian brain.     

Immune response to lipopolysaccharide in primary biliary cirrhosis and autoimmune diseases

A bacteriological aetiology is suspected to be the triggering factor in primary biliary cirrhosis. We studied lipid A, the toxic and immunogenic moiety of gram-negative bacteria lipopolysaccharide, which accumulates abnormally in Kupffer cells, hepatocytes, and biliary epithelial cells in primary biliary cirrhosis patients. Anti-lipid A antibody levels from serum samples from 36 primary biliary cirrhosis patients, drawn before and after ursodeoxycholic acid treatment, were compared to those from patients with other liver diseases (n=236), non-hepatic diseases (n=249), and healthy subjects (n=75). In primary biliary cirrhosis patients, the prevalence of IgM anti-lipid A antibodies was higher before than after ursodeoxycholic acid therapy (64% vs 22%, respectively; P<0.001). Patients with anti-lipid A antibodies had significantly higher IgM levels than those without antibodies (8.7+/-1.1 g/l vs 4.4+/-0.8 g/l, P<0.02). Total IgM levels were correlated with anti-lipid A antibody levels (r=0.65, P<0.02). After therapy, the serum IgM levels decreased significantly (P<0.03). These results indicate that bacterial antigens may participate in the observed increase of serum IgM levels, and support an aetiological role of a gut-derived endotoxin antigen in the pathogenesis of primary biliary cirrhosis.     

Stability of variables associated with the metabolic syndrome from adolescence to adulthood: the Aerobics Center Longitudinal Study.

The purpose of the study was to examine the stability of variables associated with the metabolic syndrome from adolescence to adulthood. The sample included 48 subjects from the Aerobics Center Longitudinal Study who had one clinical visit during adolescence (mean age = 15.8 years) and a follow-up visit during adulthood (mean age = 26.6 years). The following variables were considered: treadmill time to exhaustion (TM), body mass index (BMI), waist circumference (WC), percent body fat (%BF), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC:HDL-C, triglycerides (TG), glucose (GLU), and systolic (SBP), diastolic (DBP), and mean (MAP) blood pressure. A composite risk factor score using variables consistent with the WHO and ATP III definition of the metabolic syndrome (WC, HDL-C, TG, MAP, and GLU) was calculated. Tracking coefficients were computed as partial correlations, controlling for length of follow-up (mean = 11 years). Tracking coefficients (r values) were moderate for all variables (TM, 0.53; BMI, 0.64; WC; 0.79;%BF, 0.44; TC, 0.62; HDL-C, 0.60; TG, 0.54; TC:HDL-C, 0.78; SBP, 0.45; and MAP, 0.41), except GLU (0.26) and DBP (0.21). The composite risk factor score also tracked moderately well (0.56) from adolescence into adulthood. The results support previous findings that variables associated with the metabolic syndrome track moderately well from adolescence to adulthood. The findings support the prevention and treatment of obesity, atherosclerosis, type 2 diabetes, and the metabolic syndrome during childhood and adolescence.