Psychosocial factors and early childhood caries among low-income African–American children in Detroit

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75540/1/j.1600-0528.2006.00352.x.pd

Human Cataract Mutations in EPHA2 SAM Domain Alter Receptor Stability and Function

The cellular and molecular mechanisms underlying the pathogenesis of cataracts leading to visual impairment remain poorly understood. In recent studies, several mutations in the cytoplasmic sterile-α-motif (SAM) domain of human EPHA2 on chromosome 1p36 have been associated with hereditary cataracts in several families. Here, we have investigated how these SAM domain mutations affect EPHA2 activity. We showed that the SAM domain mutations dramatically destabilized the EPHA2 protein in a proteasome-dependent pathway, as evidenced by the increase of EPHA2 receptor levels in the presence of the proteasome inhibitor MG132. In addition, the expression of wild-type EPHA2 promoted the migration of the mouse lens epithelial αTN4-1 cells in the absence of ligand stimulation, whereas the mutants exhibited significantly reduced activity. In contrast, stimulation of EPHA2 with its ligand ephrin-A5 eradicates the enhancement of cell migration accompanied by Akt activation. Taken together, our studies suggest that the SAM domain of the EPHA2 protein plays critical roles in enhancing the stability of EPHA2 by modulating the proteasome-dependent process. Furthermore, activation of Akt switches EPHA2 from promoting to inhibiting cell migration upon ephrin-A5 binding. Our results provide the first report of multiple EPHA2 cataract mutations contributing to the destabilization of the receptor and causing the loss of cell migration activity

Enterocyte Shedding and Epithelial Lining Repair Following Ischemia of the Human Small Intestine Attenuate Inflammation

BACKGROUND: Recently, we observed that small-intestinal ischemia and reperfusion was found to entail a rapid loss of apoptotic and necrotic cells. This study was conducted to investigate whether the observed shedding of ischemically damaged epithelial cells affects IR induced inflammation in the human small gut. METHODS AND FINDINGS: Using a newly developed IR model of the human small intestine, the inflammatory response was studied on cellular, protein and mRNA level. Thirty patients were consecutively included. Part of the jejunum was subjected to 30 minutes of ischemia and variable reperfusion periods (mean reperfusion time 120 (+/-11) minutes). Ethical approval and informed consent were obtained. Increased plasma intestinal fatty acid binding protein (I-FABP) levels indicated loss in epithelial cell integrity in response to ischemia and reperfusion (p<0.001 vs healthy). HIF-1alpha gene expression doubled (p = 0.02) and C3 gene expression increased 4-fold (p = 0.01) over the course of IR. Gut barrier failure, assessed as LPS concentration in small bowel venous effluent blood, was not observed (p = 0.18). Additionally, mRNA expression of HO-1, IL-6, IL-8 did not alter. No increased expression of endothelial adhesion molecules, TNFalpha release, increased numbers of inflammatory cells (p = 0.71) or complement activation, assessed as activated C3 (p = 0.14), were detected in the reperfused tissue. CONCLUSIONS: In the human small intestine, thirty minutes of ischemia followed by up to 4 hours of reperfusion, does not seem to lead to an explicit inflammatory response. This may be explained by a unique mechanism of shedding of damaged enterocytes, reported for the first time by our group

Relapse prevention for addictive behaviors

The Relapse Prevention (RP) model has been a mainstay of addictions theory and treatment since its introduction three decades ago. This paper provides an overview and update of RP for addictive behaviors with a focus on developments over the last decade (2000-2010). Major treatment outcome studies and meta-analyses are summarized, as are selected empirical findings relevant to the tenets of the RP model. Notable advances in RP in the last decade include the introduction of a reformulated cognitive-behavioral model of relapse, the application of advanced statistical methods to model relapse in large randomized trials, and the development of mindfulness-based relapse prevention. We also review the emergent literature on genetic correlates of relapse following pharmacological and behavioral treatments. The continued influence of RP is evidenced by its integration in most cognitive-behavioral substance use interventions. However, the tendency to subsume RP within other treatment modalities has posed a barrier to systematic evaluation of the RP model. Overall, RP remains an influential cognitive-behavioral framework that can inform both theoretical and clinical approaches to understanding and facilitating behavior change

Nonconvulsive Status Epilepticus in Patients Suffering Spontaneous Subarachnoid Hemorrhage

Object. Nonconvulsive status epilepticus (NCSE) is an underrecognized and poorly understood complication of aneurysmal subarachnoid hemorrhage (SAH). The authors evaluated the risk factors, electroencephalographic (EEG) characteristics, hospital course, and clinical outcomes associated with NCSE in a population with SAH treated at a single institution. Methods. The hospitalization and outcome data were reviewed in 11 patients who had received a diagnosis of NCSE and SAH. The study included individuals from a cohort of 389 consecutive patients with SAH who were treated between March 2003 and June 2005, and who were analyzed retrospectively. The patients\u27 medical history, neurological grade, events of hospitalization, EEG morphological patterns, and disposition were analyzed. Advanced age, female sex, need for ventriculostomy, poor neurological grade (Hunt and Hess Grade III, IV, or V), thick cisternal blood clots, and structural lesions (intracerebral hemorrhage and stroke) were common in the population with NCSE. Patients with normal results on angiograms, good neurological grade (Hunt and Hess Grade I or II), and minimal SAH (Fisher Grade 1 or 2) were at lower risk. The most common ictal patterns were intermittent, and consisted of generalized periodic epileptiform discharges. Medical complications were also frequent, and the outcome of these patients was poor despite aggressive treatment regimens. Conclusions. Nonconvulsive status epilepticus is a devastating complication of SAH with a high rate of associated morbidity. Based on these findings it appears that the patients at highest risk for NCSE can be identified, and this should provide a basis for further studies designed to determine the clinical significance of various EEG patterns and to develop preventative strategies