Adverse childhood experiences as a predictor of attendance at a health-promotion program.

This short-term longitudinal study examined whether adverse childhood experiences predicted attendance at a fitness program. We asked undergraduates participating in a group fitness program at a university to complete measures of mental health and adverse childhood experiences at the start of the semester. Attendance data were obtained from the recreational center at the end of the semester. Adverse childhood experiences predicted attendance after parental education and mental health were taken into account. To our knowledge, this is the first study to demonstrate that more adverse childhood experiences predict lower attendance at a health-promotion program. Findings suggest a need for adverse childhood experiences screening to prevent drop-out.

The intracellular interactions of the L1 family of cell adhesion molecules.

The L1 family of CAMs (cell adhesion molecules) has long aroused the interest of researchers, but primarily the extracellular interactions of these proteins have been elucidated. More recently, attention has turned to the intracellular signalling potentiated by transmembrane proteins and the cytoplasmic proteins with which they can interact. The present review brings up to date the current body of published knowledge for the intracellular interactions of L1-CAM family proteins and the potential importance of these interactions for the mechanisms of L1-CAM action.

Expanding the Original Definition of Adverse Childhood Experiences (ACEs).

We report two studies examining psychometric properties of an expanded measure of adverse childhood experiences (ACEs) that combined the original ACEs items with items from the Juvenile Victimization Questionnaire. In Study 1, we examined its factorial structure, internal consistency, and concurrent validity in undergraduates (N = 1479). In Study 2, we also examined replicability of frequencies of ACEs, test-retest reliability, and convergent and predictive validity. Results suggested a model with four inter-related factors: maltreatment, household dysfunction, community dysfunction, and peer dysfunction/property victimization. Internal consistency, test-retest reliability, concurrent and convergent validity were acceptable, and findings were replicated across samples. We suggest that this expanded measure is assessing early experiences of victimization and helplessness in the face of perceived intentional emotional and physical threats or actual harm by others, and that although they may not all be "traumatic," their cumulative impact is associated with poor mental health in young adults.

Eliminating perioperative adverse events at Ascension Health.

BACKGROUND: For Ascension Health's Healthcare That Is Safe strategy, Sacred Heart Hospital (SHH) and Columbia St. Mary's (CSM) served as alpha sites to develop strategies to eliminate perioperative adverse events (POAEs). The alpha sites set an interim goal of a 50% reduction of POAEs, then 100%, or elimination of POAEs by July 2008. IMPLEMENTATION: The alpha sites identified a process for data management to establish clear, measurable elements for each of the five strategies of the alpha initiative; created an infrastructure to foster transformational change in the operating room suite; and implemented tactics to measure the success of the five strategies. STRATEGIES AND TACTICS: The sites implemented tactics for five strategies: (1) prevention of errors due to human factors, (2) prevention of surgical site infections, (3) prevention of adverse perioperative cardiac events, (4) prevention of postoperative venous thromboembolism, and (5) prevention of postoperative hemorrhage. RESULTS: Both alpha sites achieved > or = 90% reduction in the POAE rate. DISCUSSION: A number of key learnings were drawn from the alpha experiences, including the need to adjust to evolving definitions and guidelines for implementation and measurement of perioperative care.

Recycling of the human prostacyclin receptor is regulated through a direct interaction with Rab11a GTPase.

The human prostacyclin receptor (hIP) undergoes agonist-induced internalization but the mechanisms regulating its intracellular trafficking and/or recycling to the plasma membrane are poorly understood. Herein, we conducted a yeast-two-hybrid screen to identify proteins interacting with the carboxyl-terminal (C)-tail domain of the hIP and discovered a novel interaction with Rab11a. This interaction was confirmed by co-immunoprecipitations in mammalian HEK293 and was augmented by cicaprost stimulation. The hIP co-localized to Rab11-containing recycling endosomes in both HEK293 and endothelial EA.hy 926 cells in a time-dependent manner following cicaprost stimulation. Moreover, over-expression of Rab11a significantly increased recycling of the hIP, while the dominant negative Rab11(S25N) impaired that recycling. Conversely, while the hIP co-localized to Rab4-positive endosomes in response to cicaprost, ectopic expression of Rab4a did not substantially affect overall recycling nor did Rab4a directly interact with the hIP. The specific interaction between the hIP and Rab11a was dependent on a 22 amino acid (Val(299)-Gln(320)) sequence within its C-tail domain and was independent of isoprenylation of the hIP. This study elucidates a critical role for Rab11a in regulating trafficking of the hIP and has identified a novel Rab11 binding domain (RBD) within its C-tail domain that is both necessary and sufficient to mediate interaction with Rab11a.

Patients with a non-dysferlin Miyoshi myopathy have a novel membrane repair defect.

Two autosomal recessive muscle diseases, limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM), are caused by mutations in the dysferlin gene. These mutations result in poor ability to repair cell membrane damage, which is suggested to be the cause for this disease. However, many patients who share clinical features with MM-type muscular dystrophy do not carry mutations in dysferlin gene. To understand the basis of MM that is not due to mutations in dysferlin gene, we analyzed cells from patients in one such family. In these patients, we found no defects in several potential candidates - annexin A2, caveolin-3, myoferlin and the MMD2 locus on chromosome 10p. Similar to dysferlinopathy, these cells also exhibit membrane repair defects and the severity of the defect correlated with severity of their disease. However, unlike dysferlinopathy, none of the conventional membrane repair pathways are defective in these patient cells. These results add to the existing evidence that cell membrane repair defect may be responsible for MM-type muscular dystrophy and indicate that a previously unsuspected genetic lesion that affects cell membrane repair pathway is responsible for the disease in the non-dysferlin MM patients.

A functional FERM domain binding motif in neurofascin.

The L1 family of transmembrane cell adhesion receptors are involved in the development of the nervous system and consist of L1, neuron-glial-related cell adhesion molecule and neurofascin. All three receptors have a short cytoplasmic tail which is known to bind to the cytoskeletal associated protein ankyrin. Ezrin is a cytoplasmic binding protein known to link plasma membrane proteins to the cytoskeleton and has been shown to be a binding partner for L1. Here we show that neurofascin can also interact directly with ezrin. However, the mechanism of interaction of L1 and neurofascin with ezrin is by different mechanisms. We also show that the neurofascin isoform, Nfasc155, co-localizes with ezrin in transfected HEK293 cells but also in interdigitating Schwann cells at the node of Ranvier.

Synapse associated protein 102 is a novel binding partner to the cytoplasmic terminus of neurone-glial related cell adhesion molecule.

Neurone glial-related cell adhesion molecule (NrCAM) is a member of the L1 family of transmembrane cell adhesion receptors which are involved in the development and function of the mammalian nervous system. How these receptors interact with intracellular signalling pathways is not understood. To date the only identified binding partner to the cytoplasmic terminus of NrCAM is ankyrin G. We screened a developing rat brain cDNA yeast two-hybrid library with the cytoplasmic domain of NrCAM to identify further intracellular binding partners. We identified synapse associated protein 102 (SAP102) as a new binding partner for NrCAM. The interaction was confirmed biochemically using glutathione S-transferase (GST)-pull-down and tandem affinity purification, and also immunocytochemically as NrCAM and SAP102 co-localized in COS-7 and cerebellar granule cells. Binding was specific to NrCAM as neither neurofascin nor L1 bound SAP102, and this interaction was reliant on the last three amino acids of NrCAM. Additionally, NrCAM constructs whose last three amino acids had been deleted appeared to have a dominant negative effect on neurite extension of cerebellar granule cells. This is the first interaction reported for NrCAM, and its association with SAP102 suggests that it is part of a larger complex which can interact with many different signalling pathways.

Expression and splicing of the insulin-like growth factor gene in rodent muscle is associated with muscle satellite (stem) cell activation following local tissue damage.

Muscle satellite cells are mononuclear cells that remain in a quiescent state until activated when they proliferate and fuse with muscle fibres to donate nuclei, a process necessary for post-embryonic growth, hypertrophy and tissue repair in this post-mitotic tissue. These processes have been associated with expression of the insulin-like growth factor (IGF-I) gene that can undergo alternative splicing to generate different gene products with varying functions. To gain insight into the cellular mechanisms involved in local tissue repair, the time courses of expression of two IGF-I splice variants produced in muscle were determined together with marker genes for satellite cell activation following local muscle damage. Using real-time RT-PCR with specific primers, the mRNA transcripts in rat tibialis anterior muscles were measured at different time intervals following either mechanical damage imposed by electrical stimulation of the stretched muscle or damage caused by injection with bupivacaine. It was found that the autocrine splice variant mechano growth factor (MGF) was rapidly expressed and then declined within a few days following both types of damage. Systemic IGF-IEa was more slowly upregulated and its increase was commensurate with the rate of decline in MGF expression. Satellite cell activation as measured by M-cadherin and one of the muscle regulatory factors MyoD and the sequence of expression suggests that the initial pulse of MGF is responsible for satellite cell activation, as the systemic IGF-IEa mRNA expression peaks after the expression of these markers, including M-cadherin protein. Later splicing of the IGF-I gene away from MGF but towards IGF-IEa seems physiologically appropriate as IGF-IEa is the main source of mature IGF-I for upregulation of protein synthesis required to complete the repair.

Muscle satellite (stem) cell activation during local tissue injury and repair.

In post-mitotic tissues, damaged cells are not replaced by new cells and hence effective local tissue repair mechanisms are required. In skeletal muscle, which is a syncytium, additional nuclei are obtained from muscle satellite (stem) cells that multiply and then fuse with the damaged fibres. Although insulin-like growth factor-I (IGF-l) had been previously implicated, it is now clear that muscle expresses at least two splice variants of the IGF-I gene: a mechanosensitive, autocrine, growth factor (MGF) and one that is similar to the liver type (IGF-IEa). To investigate this activation mechanism, local damage was induced by stretch combined with electrical stimulation or injection of bupivacaine in the rat anterior tibialis muscle and the time course of regeneration followed morphologically. Satellite cell activation was studied by the distribution and levels of expression of M-cadherin (M-cad) and related to the expression of the two forms of IGF-I. It was found that the following local damage MGF expression preceded that of M-cad whereas IGF-IEa peaked later than M-cad. The evidence suggests therefore that an initial pulse of MGF expression following damage is what activates the satellite cells and that this is followed by the later expression of IGF-IEa to maintain protein synthesis to complete the repair.