Citations

Objective: The objective of this study was to investigate the importance of immigration as a risk factor for self-reported frequent mental distress (FMD) among black respondents to an Internet survey. Method: Snowball sampling was used to obtain Internet survey responses from immigrant and non-immigrant black adults in the United States. Multiple logistic regression analysis was used to control for the effects of personal characteristics ( N = 301). Results: In this sample of black adults, 13.3% had FMD. Being an immigrant was not associated with FMD in this sample (adjusted odds ratio [OR] = 0.75, P = .53). However, more drinking days was an independent risk factor (OR = 1.07, P < .01). Conclusions: Being an immigrant was not an independent risk factor for FMD in this sample of black adults. However, drinking more days per month was a significant risk factor. Primary care providers should be alert for FMD and alcohol consumption in this population. Directing health education about hazardous drinking toward high-risk individuals should be considered.

The family history is used as a screening tool to identify persons who may be at risk for a heritable disorder. Primary care providers sometimes do not thoroughly gather and document the family history. This pilot study was undertaken to determine whether having a genetic counselor on site at our family medicine clinic 2 days a week for 3 months would improve the quality of the family history field in patient records. We compared 7 elements in the family history field for patients seen before and after the genetic counselor was on site. Documentation of 1 of the 7 elements (major disease) improved significantly after the intervention period ( P = .02). Changing provider behavior with regard to gathering and documenting family history of major disease may be facilitated by tools to help collect the family history and by using the increasing number of available genetic tests.

ABSTRACTBackground:Although direct medical costs for constipation‐related medical visits are thought to be high, to date there have been no studies examining whether longitudinal resource use is persistently elevated in children with constipation. Our aim was to estimate the incremental direct medical costs and types of health care use associated with constipation from childhood to early adulthood.Methods:A nested case‐control study was conducted to evaluate the incremental costs associated with constipation. The original sample consisted of 5718 children in a population‐based birth cohort who were born during 1976 to 1982 in Rochester, MN. The cases included individuals who presented to medical facilities with constipation. The controls were matched and randomly selected among all noncases in the sample. Direct medical costs for cases and controls were collected from the time subjects were between 5 and 18 years of age or until the subject emigrated from the community.Results:We identified 250 cases with a diagnosis of constipation in the birth cohort. Although the mean inpatient costs for cases were $9994 (95% Confidence interval [CI] 2538–37,201) compared with $2391 (95% CI 923–7452) for controls (P = 0.22) during the time period, the mean outpatient costs for cases were $13,927 (95% CI 11,325–16,525) compared with $3448 (95% CI 3771–4621) for controls (P < 0.001) during the same time period. The mean annual number of emergency department visits for cases was 0.66 (95% CI 0.62–0.70) compared with 0.34 (95% CI 0.32–0.35) for controls (P < 0.0001).Conclusions:Individuals with constipation have higher medical care use. Outpatient costs and emergency department use were significantly greater for individuals with constipation from childhood to early adulthood.

Transforming growth factor (TGF)-β family proteins form heteromeric complexes with transmembrane serine/threonine kinases referred to as type I and type II receptors. Ligand binding initiates a signaling cascade that generates a variety of cell type-specific phenotypes. Whereas numerous studies have investigated the regulatory activities controlling TGF-β signaling, there is relatively little information addressing the endocytic and trafficking itinerary of TGF-β receptor subunits. In the current study we have investigated the role of the clathrin-associated sorting protein Disabled-2 (Dab2) in TGF-β receptor endocytosis. Although small interfering RNA-mediated Dab2 knockdown had no affect on the internalization of various clathrin-dependent (i.e., TGF-β, low-density lipoprotein, or transferrin) or -independent (i.e., LacCer) cargo, TGF-β receptor recycling was abrogated. Loss of Dab2 resulted in enlarged early endosomal antigen 1-positive endosomes, reflecting the inability of cargo to traffic from the early endosome to the endosomal recycling compartment and, as documented previously, diminished Smad2 phosphorylation. The results support a model whereby Dab2 acts as a multifunctional adaptor in mesenchymal cells required for TGF-β receptor recycling as well as Smad2 phosphorylation.

Neointimal hyperplasia contributes to failure of hemodialysis arteriovenous fistulas (AVFs). Increased expression of matrix metalloproteinase (MMP)-9 occurs in AVFs, and MMP-9 is implicated in neointimal hyperplasia and vascular injury. Recent studies demonstrate that MMP-9, by degrading N-cadherin, leads to increased expression of β-catenin and β-catenin-dependent proliferation of smooth muscle cells. The present study examined this pathway in the venous limb of a murine AVF model. Western analyses demonstrate that, in this model, there is diminished expression of N-cadherin accompanied by increased expression of β-catenin, c-Myc, and proliferating cell nuclear antigen (PCNA). By immunohistochemistry, β-catenin and c-Myc localized to proliferating smooth muscle cells in the venous limb of the AVF. Increased expression of β-catenin was accompanied by augmented expression of phosphorylated (p)-glycogen synthase kinase (GSK)-3β, GSK-3β, and integrin-linked kinase. The administration of doxycycline suppressed MMP-9 expression but did not reduce venous histological injury in the AVF, or increase AVF patency assessed 6 wk after its creation. Doxycycline did not influence expression of β-catenin, c-Myc, GSK-3β, or integrin-linked kinase. Thus, in this vascular injury model, the upregulation of β-catenin cannot be readily attributed to MMP-9 upregulation; increased β-catenin expression may reflect either the upregulation of p-GSK-3β, GSK-3β, or integrin-linked kinase. This study provides the first exploration of β-catenin in an AVF, demonstrating substantial upregulation of this mitogenic signaling molecule and uncovering possible mechanisms that may account for such upregulation.

Abstract A critical problem in the treatment of malignant gliomas is the extensive infiltration of individual tumor cells into adjacent brain tissues. This invasive phenotype severely limits all current therapies, and to date, no treatment is available to control the spread of this disease. Members of the tumor necrosis factor (TNF) ligand superfamily and their cognate receptors regulate various cellular responses including proliferation, migration, differentiation, and apoptosis. Specifically, the TNFRSF19/TROY gene encodes a type I cell surface receptor that is expressed on migrating or proliferating progenitor cells of the hippocampus, thalamus, and cerebral cortex. Here, we show that levels of TROY mRNA expression directly correlate with increasing glial tumor grade. Among malignant gliomas, TROY expression correlates inversely with overall patient survival. In addition, we show that TROY overexpression in glioma cells activates Rac1 signaling in a Pyk2-dependent manner to drive glioma cell invasion and migration. Pyk2 coimmunoprecipitates with the TROY receptor, and depletion of Pyk2 expression by short hairpin RNA interference oligonucleotides inhibits TROY-induced Rac1 activation and subsequent cellular migration. These findings position aberrant expression and/or signaling by TROY as a contributor, and possibly as a driver, of the malignant dispersion of glioma cells. Mol Cancer Res; 8(11); 1558–67. ©2010 AACR.

OBJECTIVE. Fatigue is a common, troublesome symptom for persons with multiple sclerosis. This study evaluated the effects of an energy conservation course on fatigue impact for persons with multiple sclerosis whose symptoms cause moderate to severe disability. METHODS. Thirty-seven persons with progressive multiple sclerosis participated in an 8-week experimental energy conservation course treatment and an 8-week control period of traditional treatment using a crossover design. The Fatigue Impact Scale (FIS) was used to assess fatigue impact before and after the experimental and control periods, and 8 weeks post-energy conservation course. RESULTS. After participation in the energy conservation course, the average FIS total score and physical, cognitive, and psychosocial subscale scores decreased significantly, whereas the total and subscale scores did not change significantly during the control period. Additionally, decreased fatigue impact was maintained 8 weeks after course completion for evaluated participants. CONCLUSION. This study provides evidence that this energy conservation course can be a beneficial intervention for persons with progressive multiple sclerosis.