Self-Coding of Fidelity as a Potential Active Ingredient of Consultation to Improve Clinicians’ Fidelity

A key goal for implementation science is the identification of evidence-based consultation protocols and the active ingredients within these protocols that drive clinician behavior change. The current study examined clinicians’ self-coding of fidelity as a potential active ingredient of consultation for the Attachment and Biobehavioral Catch-up (ABC) intervention. It also examined two other potential predictors of clinician fidelity in response to consultation: dosage of consultation and working alliance. Twenty-nine clinicians (97% female, 62% White, M age?=?34 years) participated in a year of weekly fidelity-focused ABC consultation sessions, for which clinicians self-coded fidelity and received consultant feedback on both their coding and their fidelity. Data from the ABC fidelity measure were available for 1067 sessions coded by consultants, and clinicians’ self-coding accuracy was calculated from 1044 sessions coded by both clinicians and consultants. Alliance was measured with the Working Alliance Inventory—Trainee and Supervisor Versions. The study was observational, and fidelity and self-coding accuracy were modeled across time using hierarchical linear modeling. Clinicians’ ABC fidelity, as well as their self-coding accuracy, increased over the course of consultation. Clinicians’ self-coding accuracy predicted their initial fidelity and growth in fidelity. Working alliance was also linked to fidelity and self-coding accuracy. These results suggest that clinician self-coding should be further examined as an active ingredient of consultation. The study has important implications for the design of consultation procedures and fidelity assessments.

     

Motor activity and neurotransmitter release in the gastric fundus of streptozotocin-diabetic rats.

As deficiencies of the cholinergic and non-adrenergic non-cholinergic innervation of the gastrointestinal tract have been described in diabetic rats, we studied the simultaneous release of, and muscular response to, acetylcholine, vasoactive intestinal polypeptide and adenosine-5'-triphosphate in isolated preparations of gastric fundus from control and 8-week streptozotocin-treated diabetic rats. Muscular responses were measured in longitudinal muscle strips prepared from one half of the gastric fundus and release was studied in the other half. The contractile response to acetylcholine and electrical field stimulation was not different in control and diabetic rats. In the presence of atropine, and when tone was increased with prostaglandin F2 alpha, electrical field stimulation, vasoactive intestinal polypeptide and adenosine-5'-triphosphate induced relaxation with a similar response in control and diabetic rats. The basal release of acetylcholine, vasoactive intestinal polypeptide and adenosine-5'-triphosphate was not significantly different in control and diabetic rats. Electrical field stimulation significantly increased the release of the three substances and this increase was tetrodotoxin-sensitive. While the stimulation-induced increase of acetylcholine and vasoactive intestinal polypeptide was not different in control and in diabetic rats, the stimulation-induced release of adenosine-5'-triphosphate increased 3-fold in diabetic compared to control gastric fundus. Desensitization to alpha,beta-methylene adenosine-5'-triphosphate reduced the relaxant response to adenosine-5'-triphosphate and to electrical field stimulation, suggesting a role of adenosine-5'-triphosphate in non-adrenergic non-cholinergic neurotransmission of rat gastric fundus. The reduction of the non-adrenergic non-cholinergic relaxation by alpha,beta-methylene adenosine-5'-triphosphate was greater in diabetic tissues. This, with the increase in stimulation-induced adenosine-5'-triphosphate release, suggests that the purinergic component of the vagal non-adrenergic non-cholinergic response of the stomach may be increased in diabetics.     

Restoration of diabetes-induced changes in enteric nerves by phorbol 12,13-dibutyrate.

Treatment of segments of ileum from 8-week streptozotocin-induced diabetic rats with phorbol 12,13-dibutyrate (PDBu) in vitro resulted in restoration of the diabetes-induced changes in the expression of enteric VIP- and galanin-like immunoreactive nerve fibres. The increase in fluorescence intensity and density of VIP- and galanin-like immunoreactivity observed in 8-week streptozotocin-treated rats was reduced to a near normal level after 40 min incubation of diabetic tissues in Krebs solution containing PDBu (100 nM). The tissue content of VIP was also affected (control = 2.1 +/- 0.31 pmol/cm; diabetic = 4.6 +/- 0.48 pmol/cm; diabetic + PDBu = 2.9 +/- 0.91 pmol/cm) after incubation with PDBu. The significance of these findings in relation to the possible role of protein kinase C in the regulation of expression and/or storage of these enteric neuropeptides in normal and diabetic states is discussed.     

CTLA-4 is required for the induction of high dose oral tolerance

Mucosal and systemic administrations of high dose antigens induce long- lasting peripheral T cell tolerance. We and others have shown that high dose peripheral T cell tolerance is mediated by anergy or deletion and is preceded by T cell activation. Co-stimulatory molecules B7-1 (CD80)/B7-2 (CD86) and their counter-receptors CD28/CTLA-4 play pivotal roles in T cell activation and immune regulation. In the present study, we examined the roles of the B7 co-stimulation pathway in the generation of high dose peripheral T cell tolerance. We found that blocking B7:CD28/CTLA-4 interaction at the time of tolerance induction partially prevented T cell tolerance, whereas selective blockade of B7:CTLA-4 interaction completely abrogated peripheral T cell tolerance induced by either oral or i.p. antigens. These results suggest that CTLA-4-mediated feedback regulation plays a crucial role in the induction of high dose peripheral T cell tolerance.      

Pattern of distribution and co-localization of NOS and ATP in the myenteric plexus of human fetal stomach and intestine

The pattern of distribution and co-localization of nitric oxide synthase (NOS) and quinacrine fluorescence (indicative of vesicular adenosine 5'-triphosphate, ATP), and co-localization of NADPH-diaphorase (NADPH-d) activity and NOS-immunoreactivity in the myenteric plexus of pre-term human fetal (6-17 weeks of gestation) stomach and small intestine was examined using immunohistochemical and histochemical techniques. In all stages of gestation investigated, NOS-immunoreactive and NADPH-d-reactive myenteric neurons and nerve fibres were seen in the fetal intestine and stomach. However, in fetuses of 6-10 weeks of gestation, only 15% of the NADPH-d-positive myenteric neurons were NOS-immunoreactive, whereas a 100% co-localization was found in samples of 12-17 weeks of gestation. Quinacrine fluorescent myenteric neurons and nerve fibres were found only in the fetal intestine of 12-17 weeks of gestation, of which 25% of the NADPH-d-positive myenteric neurons in these samples were quinacrine fluorescent. These findings demonstrate the presence and co-localization of markers for nitric oxide (NO)- and ATP-utilizing myenteric neurons and nerve fibres in the early stages of gestation, suggesting possible co-transmitter and/or trophic roles of ATP and NO in the process of development and maturity of human myenteric neurons. In addition, the fact that only a small percentage of NADPH-d-reactive myenteric neurons express NOS immunoreactivity at 6-10 weeks of gestation confirms that NADPH-d-reactivity does not always represent NOS activity.     

Correlations between Oxidative DNA Damage, Oxidative Stress and Coenzyme Q10 in Patients with Coronary Artery Disease

The correlation of coronary artery disease (CAD) with pro-oxidant/antioxidant balance and oxidative DNA damage was investigated.Seventy-seven patients with CAD and 44 healthy individuals as control were included in this study. The comparative ratios of ubiquinol-10/ubiquinone-10, 8-hydroxy-2^''-deoxyguanosine/deoxyguanosine and the level of MDA measured by HPLC and the activities of GPX and SOD by colorimetric approach in blood samples obtained from patients with CAD were unraveled.8-OHdG/dG ratios, serum MDA level and GPX activity were found significantly elevated level in serum of CAD patients compared to control group. The SOD activity was observed in stable levels in CAD patients. Ubiquinol-10/ubiquinone-10 ratio was significantly lower in patients with CAD than the controls.The positive correlation was observed between 8-OHdG/dG ratios in both MDA levels and GPX activity, while the significant negative correlation was seemed between the ratio of 8-OHdG/dG and ubiquinol-10/ ubiquinone-10 as well as MDA levels and ubiquinol-10/ ubiquinone-10 ratio.We conclude that, both the disruption of pro-oxidant/antioxidant balance and oxidative stress in DNA may play an important role in the pathogenesis of coronary artery disease.     

Beta 2-integrin and L-selectin are obligatory receptors in neutrophil aggregation [see comments]

We have recently found that antibodies to L-selectin, the homing receptor on neutrophils, are as effective as those to beta 2-integrin at blocking formyl peptide-stimulated aggregation. Therefore, we investigated the requirements for expression of L-selectin and beta 2- integrin on adjacent cells during aggregation. Fluorescence flow cytometry allowed characterization of aggregates on the basis of size and color, as well as antibody binding to these two adhesive molecules. Formyl peptide-stimulated aggregate formation was measured for individual populations fluorescently labeled red (LDS-751) or green (CD44-FITC), and interpopulation red-green cell conjugates. Blocking either the beta 2-integrin or L-selectin adhesive epitope with monoclonal antibody on individual cell populations resulted in an approximately 50% reduction in two-color aggregation as compared with that in unblocked samples. Shedding the L-selectin on a cell population by preincubation with complexes of lipopolysaccharide and its plasma membrane binding protein also decreased aggregation to a control population by approximately 50%. We examined the aggregation of neutrophils from patients genetically deficient in beta 2-integrin and clinically leukocyte adhesion deficient (LAD). LAD adhesion to normal neutrophils was dependent on the expression of L-selectin on LAD cells and beta 2-integrin on normal cells. Thus, the minimum requirement for adhesion between two mixed populations of neutrophils was that one population expressed the beta 2-integrin and the other expressed the L- selectin adhesive epitope.