More than synaptic plasticity: role of nonsynaptic plasticity in learning and memory.

Decades of research on the cellular mechanisms of memory have led to the widely held view that memories are stored as modifications of synaptic strength. These changes involve presynaptic processes, such as direct modulation of the release machinery, or postsynaptic processes, such as modulation of receptor properties. Parallel studies have revealed that memories might also be stored by nonsynaptic processes, such as modulation of voltage-dependent membrane conductances, which are expressed as changes in neuronal excitability. Although in some cases nonsynaptic changes can function as part of the engram itself, they might also serve as mechanisms through which a neural circuit is set to a permissive state to facilitate synaptic modifications that are necessary for memory storage.

Development and testing of a procedure for systematically assigning gestational age for clinical and research use

A graphing method was developed and tested to estimate gestational ages pre-and postnatally in a consistent manner for epidemiological research and clinical purposes on feti/infants of women with few consistent prenatal estimators of gestational age. Each patient's available data was plotted on a single page graph to give a comprehensive overview of that patient. A hierarchical classification of gestational age determination was then applied in a systematic manner, and reasonable gestational age estimates were produced. The method was tested for validity and reliability on 50 women who had known dates for their last menstrual period or dates of conception, and multiple ultrasound examinations and other gestational age estimating measures. The feasibility of the procedure was then tested on 1223 low income women with few gestational age estimators. The graphing method proved to have high inter- and intrarater reliability. It was quick, easy to use, inexpensive, and did not require special equipment. The graphing method estimate of gestational age for each infant was tested against the last menstrual period gestational age estimate using paired t-Tests, F tests and the Kolmogorov-Smirnov test of similar populations, producing a 98 percent probability or better that the means and data populations were the same. Less than 5 percent of the infants' gestational ages were misclassified using the graphing method, much lower than the amount of misclassification produced by ultrasound or neonatal examination estimates. ^

Risk, outcomes, and cost of emergency center visits in cancer patients

Cancer is a chronic disease that often necessitates recurrent hospitalizations, a costly pattern of medical care utilization. In chronically ill patients, most readmissions are for treatment of the same condition that caused the preceding hospitalization. There is concern that rather than reducing costs, earlier discharge may shift costs from the initial hospitalization to emergency center visits. ^ This is the first descriptive study to measure the incidence of emergency center visits (ECVs) after hospitalization at The University of M. D. Anderson Cancer Center (UTMDACC), to identify the risk factors for and outcomes of these ECVs, and to compare 30-day all-cause mortality and costs for episodes of care with and without ECVs. ^ We identified all hospitalizations at UTMDACC with admission dates from September 1, 1993 through August 31, 1997 which met inclusion criteria. Data were electronically obtained primarily from UTMDACC's institutional database. Demographic factors, clinical factors, duration of the index hospitalization, method of payment for care, and year of hospitalization study were variables determined for each hospitalization. ^ The overall incidence of ECVs was 18%. Forty-five percent of ECVs resulted in hospital readmission (8% of all hospitalizations). In 1% of ECVs the patient died in the emergency center, and for the remaining 54% of ECVs the patient was discharged home. Risk factors for ECVs were marital status, type of index hospitalization, cancer type, and duration of the index hospitalization. The overall 30-day all-cause mortality rate was 8.6% for hospitalizations with an ECV and 5.3% for those without an ECV. In all subgroups, the 30-day all-cause mortality rate was higher for groups with ECVs than for those without ECVs. The most important factor increasing cost was having an ECV. In all patient subgroups, the cost per episode of care with an ECV was at least 1.9 times the cost per episode without an ECV. ^ The higher costs and poorer outcomes of episodes of care with ECVs and hospital readmissions suggest that interventions to avoid these ECVs or mitigate their costs are needed. Further research is needed to improve understanding of the methodological issues involved in relation to health care issues for cancer patients. ^

Role of entorhinal cortical plasticity in spatial and contextual memory

It is well accepted that the hippocampus (HIP) is important for spatial and contextual memories, however, it is not clear if the entorhinal cortex (EC), the main input/output structure for the hippocampus, is also necessary for memory storage. Damage to the EC in humans results in memory deficits. However, animal studies report conflicting results on whether the EC is necessary for spatial and contextual memory. Memory consolidation requires gene expression and protein synthesis, mediated by signaling cascades and transcription factors. Extracellular-signal regulated kinase (ERK) cascade activity is necessary for long-term memory in several tasks, including those that test spatial and contextual memory. In this work, we explore the role of ERK-mediated plasticity in the EC on spatial and contextual memory. ^ To evaluate this role, post-training infusions of reversible pharmacological inhibitors specific for the ERK cascade that do not affect normal neuronal activity were targeted directly to the EC of awake, behaving animals. This technique provides spatial and temporal control over the inhibition of the ERK cascade without affecting performance during training or testing. Using the Morris water maze to study spatial memory, we found that ERK inhibition in the EC resulted in long-term memory deficits consistent with a loss of spatial strategy information. When animals were allowed to learn and consolidate a spatial strategy for solving the task prior to training and ERK inhibition, the deficit was alleviated. To study contextual memory, we trained animals in a cued fear-conditioning task and saw an increase in the activation of ERK in the EC 90 minutes following training. ERK inhibition in the EC over this time point, but not at an earlier time point, resulted in increased freezing to the context, but not to the tone, during a 48-hour retention test. In addition, animals froze maximally at the time the shock was given during training; similar to naïve animals receiving additional training, suggesting that ERK-mediated plasticity in the EC normally suppresses the temporal nature of the freezing response. These findings demonstrate that plasticity in the EC is necessary for both spatial and contextual memory, specifically in the retention of behavioral strategies. ^

Exploring parents' memories of their child's death related sensory experiences as a dimension of grieving

Little is known about how dying children and their parents experience death. Dying children have reported death related sensory experiences (DRSEs), defined as seeing or hearing someone or something not visible or audible to others, associated with dying. Although parents report that they and the dying child benefit from these experiences, healthcare providers often unknowingly dismiss them. The aims of this phenomenological inquiry were to describe children's DRSEs and their meaning from the parents' perspectives. Four fathers and six mothers of African American, Caucasian, or Hispanic ethnicity, all Christian, ranging in age from 35 to 59 years, whose child died 23 to 52 months prior and was treated at a children's cancer center, were interviewed in the home or hospital setting of their choice. Children's ages at the time of their death ranged from 4 to 13 years. A modification of van Kaarn's phenomenological method of analysis was used to analyze data. Themes emerging from the data for the first aim were: perceiving someone or something from a spiritual realm others could not, expressing awareness tempered by parental reactions, and embracing transcendence. Themes emerging from the data for the second aim were: spiritual beings prepared child; child revealed reality, preparing parents; and child transcended wholly, easing parents' grief. Post-interview surveys revealed that parents found participating in this study a "very positive" or "positive" experience, particularly being able to tell the story of their child. Children's DRSEs have clinical implications for all who provide care near the end of life. Informing parents of DRSEs, cautioning that not all dying children express them, may help parents to anticipate this phenomenon, which may decrease anxiety when their child expresses them, increasing the opportunity for open dialogue between parent and child about dying and death, and decrease regrets associated with being unreceptive to their child's expressions of death awareness. Validating a child's DRSE can have profound effects on bereaved parents. Examining DRSEs from the child's perspective and the influence of informing parents of DRSEs on the dying experience of the child and the parental grieving process are recommended. ^

The identification and prevalence of veterinary clinical events in U.S. military working dogs deployed to Iraq between March 20, 2003, and December 31, 2007

Objective. The purpose of this study was to identify the medical issues experienced by Military Working Dogs during their period of deployment in Iraq.^ Design. This study was a retrospective cross-sectional survey based on database and medical record abstraction.^ Population. Military Working Dogs (MWDs) that were deployed to Iraq at any time between 20 March 2003 and 31 December 2007 were the inclusive population of interest. Seven hundred ninety-five (795) MWDs were identified as having been deployed to Iraq during the inclusive dates. Four hundred ninety-six (496) MWDs were identified that had medical events during the deployment period. ^ Procedures. Eligible MWDs were identified through several sources, to include database query, medical record abstraction questionnaire, and medical record abstraction. Demographic information collected for each MWD included tattoo, name, age, gender, breed, Branch of Service, and duty certification. Information on each veterinary/medical clinical event (VCE) was collected. This information was coded, and data entered into a database for organization. Frequency and prevalence information were determined for each category of VCE.^ Results. The top four VCEs experienced by MWDs while deployed in Iraq were gastrohepatic, dermatologic, traumatic injury, and appendicular musculoskeletal issues.^ Conclusions. Training, equipment, and supplies for veterinary personnel who care for the deployed MWDs should be tailored accordingly to suit the identified medical needs of the MWDs. ^

The association between maternal use of selective serotonin reuptake inhibitors during pregnancy and adverse pregnancy outcomes

Maternal use of SSRIs for depression and anxiety during pregnancy has increased over the last decade. Recent studies have questioned the safety of these antidepressants when used in during pregnancy. The aim of this project is to assess the associations between maternal SSRI use and GH, SGA, and preterm birth using data from a U.S. population-based study with self-reported exposure information. ^ The study population is comprised of mothers of control infants from the NBDPS, an ongoing, multi-state, population-based case-control study. Mothers were asked about any use of medications during pregnancy, including the dates they started and stopped taking each medication. Maternal GH was self-reported, while gestational age and birth weight were calculated from information on birth certificates or medical records. ^ Our study found that women exposed to SSRIs in the first trimester and beyond had a higher odds of GH compared to unexposed women (aOR=1.96, 95% CI=1.02-3.74). Women who used SSRIs only in the first trimester had no increased odds of GH (aOR=0.77, 95% CI=0.24-2.50). Women who used SSRIs throughout their entire pregnancy had a two-fold increase in the odds of delivering an SGA infant compared to unexposed women (aOR=2.16, 95% CI=1.01-4.62), while women who reported SSRI use only in the first trimester had a decreased odds of delivering an SGA infant (aOR=0.56, 95% CI=0.14-2.34). Finally, both women who used SSRIs in the first trimester only (aOR=1.58, 95% CI=0.71-3.51) and women who used SSRIs in the first trimester and beyond (aOR=1.49, 95% CI=0.76-2.90) had an increased odds of delivering preterm compared to unexposed women. ^ Results from our study suggest that women who use SSRIs in the first trimester and beyond have an increased and significant odds of GH and SGA. An increase in the odds of preterm birth was also observed among women exposed in this period and is consistent with the results of previous studies which had much larger sample sizes. Women who use SSRIs only in the first trimester appear to have no increased odds of GH or SGA, but may have an increased odds of preterm birth. These findings are consistent with previous studies and highlight how exposure to SSRIs at different points in gestation may result in different risks for these outcomes. ^