Point of decision signs and stair use in a university worksite setting: General versus specific messages

Point-of-decision signs to promote stair use have been found to be effective in various environments. However, these signs have been more consistently successful in public access settings that use escalators, such as shopping centers and transportation stations, compared to worksite settings, which are more likely to contain elevators that are not directly adjacent to the stairs. Therefore, this study tested the effectiveness of two point-of-decision sign prompts to increase stair use in a university worksite setting. Also, this study investigated the importance of the message content of the signs. One sign displayed a general health promotion message, while the other sign presented more specific information. Overall, this project examined whether the presence of the point-of-decision signs increases stair use. In addition, this research determined whether the general or specific sign promotes greater stair use. ^ Inconspicuous observers measured stair use both before the signs were present and while they were posted. The study setting was the University of Texas School of Nursing, and the target population was anyone who entered the building, including employees, students, and visitors. The study was conducted over six weeks and included two weeks of baseline measurement, two weeks with the general sign posted, and two weeks with the specific sign posted. Each sign was displayed on a stand in the decision point area near the stairs and the elevator. Logistic regression was used to analyze the data. ^ After adjustment for covariates, the odds of stair use were significantly greater during the intervention period than the baseline period. Furthermore, the specific sign period showed significantly greater odds of stair use than the general sign period. These results indicate that a point-of-decision sign intervention can be effective at promoting stair use in a university worksite setting and that a sign with a specific health information message may be more effective at promoting stair use than a sign with a general health promotion message. These findings can be considered when planning future worksite and university based stair promotion interventions.^

Immune recognition of self nucleic acids driven by endogenous antimicrobial peptides: role in autoimmunity

Innate immune recognition of extracellular host-derived self-DNA and self-RNA is prevented by endosomal seclusion of the Toll-like receptors (TLRs) in the dendritic cells (DCs). However, in psoriasis plasmacytoid dendritic cells have been found to be able to sense self-DNA molecules in complex with the endogenous cationic antimicrobial peptide LL37, which are internalized into the endosomal compartments and thus can access TLR9. We investigated whether this endogenous peptide can also interact with extracellular self-RNA and lead to DC activation. We found that LL37 binds self-RNA as well as self-DNA going into an electrostatic interaction; forms micro-aggregates of nano-scale particles protected from enzymatic degradation and transport it into the endosomal compartments of both plasmacytoid and myeloid dendritic cells. In the plasmacytoid DCs, the self-RNA-LL37 complexes activate TLR7 and like the self-DNA-LL37 complexes, trigger the production of IFN-α in the absence of induction of maturation or production of IL-6 and TNF-α. In contrast to the self-DNA-LL37 complexes, the self-RNA-LL37 complexes are also internalized into the endosomal compartments of myeloid dendritic cells and trigger activation through TLR8, leading to the production of TNF-α and IL-6, and the maturation of the myeloid DCs. Furthermore, we found that these self nucleic acid-LL37 complexes can be found in vivo in the skin lesions of the cutaneous autoimmune disease psoriasis, where they are associated with mature mDCs in situ. On the other hand, in the systemic autoimmune disease systemic lupus erythematosus, self-DNA-LL37 complexes were found to be a constituent of the circulating immune complexes isolated from patient sera. This interaction between the endogenous peptide with the self nucleic acid molecules present in the immune complexes was found to be electrostatic and it confers resistance to enzymatic degradation of the nucleic acid molecules in the immune complexes. Moreover, autoantibodies to these endogenous peptides were found to trigger neutrophil activation and release of neutrophil extracellular traps composed of DNA, which are potential sources of the self nucleic acid-LL37 complexes present in SLE immune complexes. Our results demonstrate that the cationic antimicrobial peptide LL37 drives the innate immune recognition of self nucleic acid molecules through toll-like receptors in human dendritic cells, thus elucidating a pathway for innate sensing of host cell death. This pathway of autoreactivity was found to be pathologically relevant in human autoimmune diseases psoriasis and SLE, and thus this study provides new insights into the mechanisms autoimmune diseases.

Regulation of hepatic cytochrome P450 expression in mice with intestinal or systemic infections of citrobacter rodentium.

We reported previously that infection of C3H/HeOuJ (HeOu) mice with the murine intestinal pathogen Citrobacter rodentium caused a selective modulation of hepatic cytochrome P450 (P450) gene expression in the liver that was independent of the Toll-like receptor 4. However, HeOu mice are much more sensitive to the pathogenic effects of C. rodentium infection, and the P450 down-regulation was associated with significant morbidity in the animals. Here, we report that oral infection of C57BL/6 mice with C. rodentium, which produced only mild clinical signs and symptoms, produced very similar effects on hepatic P450 expression in this strain. As in HeOu mice, CYP4A mRNAs and proteins were among the most sensitive to down-regulation, whereas CYP4F18 was induced. CYP2D9 mRNA was also induced 8- to 9-fold in the C57BL/6 mice. The time course of P450 regulation followed that of colonic inflammation and bacterial colonization, peaking at 7 to 10 days after infection and returning to normal at 15 to 24 days as the infection resolved. These changes also correlated with the time course of significant elevations in the serum of the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha, as well as of interferon-gamma and IL-2, with serum levels of IL-6 being markedly higher than those of the other cytokines. Intraperitoneal administration of C. rodentium produced a rapid down-regulation of P450 enzymes that was quantitatively and qualitatively different from that of oral infection, although CYP2D9 was induced in both models, suggesting that the effects of oral infection on the liver are not due to bacterial translocation.

POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders.

PURPOSE: To review our clinical experience and determine if there are appropriate signs and symptoms to consider POLG sequencing prior to valproic acid (VPA) dosing in patients with seizures. METHODS: Four patients who developed VPA-induced hepatotoxicity were examined for POLG sequence variations. A subsequent chart review was used to describe clinical course prior to and after VPA dosing. RESULTS: Four patients of multiple different ethnicities, age 3-18 years, developed VPA-induced hepatotoxicity. All were given VPA due to intractable partial seizures. Three of the patients had developed epilepsia partialis continua. The time from VPA exposure to liver failure was between 2 and 3 months. Liver failure was reversible in one patient. Molecular studies revealed homozygous p.R597W or p.A467T mutations in two patients. The other two patients showed compound heterozygous mutations, p.A467T/p.Q68X and p.L83P/p.G888S. Clinical findings and POLG mutations were diagnostic of Alpers-Huttenlocher syndrome. CONCLUSION: Our cases underscore several important findings: POLG mutations have been observed in every ethnic group studied to date; early predominance of epileptiform discharges over the occipital region is common in POLG-induced epilepsy; the EEG and MRI findings varying between patients and stages of the disease; and VPA dosing at any stage of Alpers-Huttenlocher syndrome can precipitate liver failure. Our data support an emerging proposal that POLG gene testing should be considered in any child or adolescent who presents or develops intractable seizures with or without status epilepticus or epilepsia partialis continua, particularly when there is a history of psychomotor regression.

'Your Heart Can't Wait'---A worksite program: Increasing the effectiveness of worksite coordinators to implement a community-wide health education program

A worksite health education program called “Your Heart Can't Wait,” was designed by the American Heart Association Gulf Coast Area (AHA). The objectives were to educate individuals about the signs and symptoms of heart attacks and the actions they should take to improve heart attack victims' chances for survival. AHA volunteers agreed to serve as mentors for this program. ^ A study was designed to determine if worksite coordinators who had the assistance of experienced AHA volunteers had higher rates of program adoption and implementation than worksite coordinators without assistance. Ninety-seven companies participated in the study. Twelve AHA volunteers were randomly assigned to work with forty-three of the worksite coordinators. Mentor/mentee contact forms were used to assess the mentoring process during the course of the study. Program adoption forms were used to measure rates of program adoption and follow-up questionnaires were used to measure rates of program implementation after the study was completed. The twelve mentors were interviewed to provide information for improving future mentoring efforts. ^ Thirty-eight companies completed program adoption forms and fifty-one companies reported using YHCW program components. For the most part, the volunteer mentors did not spend a significant amount of time contacting or working with their assigned worksite coordinators. As a result, the planned analysis comparing the implemented programs between worksite coordinators with and without assistance could not be completed. ^ Additional analyses were performed comparing the implemented programs based upon whether the companies had existing health education/health promotion programs and whether the worksite coordinators had experience using AHA Heart At Work program components. ^ Recommendations based on the mentor interviews were made to improve the success of volunteer assistance programs in the future. ^

Predictors of survival in Alzheimer's disease

Alzheimer's disease (AD) is associated with greater mortality and reduced survival among individuals with Alzheimer's disease as compared to those without dementia. It is uncertain how these survival estimates change when the clinical signs and/or symptoms of comorbid conditions are present in individuals' with Alzheimer's disease. Cardiovascular risk factors such as hypertension, hyperlipidemia, congestive heart failure, coronary artery disease, and diabetes mellitus are common conditions in the aged population. Independently, these factors influence mortality and may have an additive effect on reduced survival in an individual with concomitant Alzheimer's disease. The bulk of the evidence from previous research efforts suggests an association between vascular co-morbidities and Alzheimer's disease incidence, but their role in survival remains to be elucidated. The objective of this proposed study was to examine the effects of cardiovascular comorbidities on the survival experience of individuals with probable Alzheimer's disease in order to identify prognostic factors for life expectancy following onset of disease. This study utilized data from the Baylor College of Medicine Alzheimer's Disease Center (ADC) longitudinal study of Alzheimer's disease and other memory disorders. Individuals between the ages of 55-69, 70-79, and ≥80 had a median survival from date of onset of 9.2 years, 8.0 years, and 7.2 years, respectively (p<0.001) and 5.5 years, 4.3 years, and 3.4 years from diagnosis. Sex was the strongest predictor of death from onset of AD, with females having a 30 percent lower risk compared to males. These findings further support the notion that age (both from onset and from diagnosis) and sex are the strongest predictors of survival among those with AD. ^

The epidemiology of dengue among children less than 18 months of age in Puerto Rico, 1999--2011

Between 1999 and 2011, 4,178 suspected dengue cases in children less than 18 months of age were reported to the Centers for Disease Control and Prevention Dengue Branch in Puerto Rico. Of the 4,178, 813 were determined to be laboratory-positive and 737 laboratory-negative. Those remaining were either laboratory-indeterminate, not processed or positive for Leptospira . On average, 63 laboratory-positive cases were reported per year. Laboratory-positive cases had a median age of 8.5 months. Among these cases, the median age for those with dengue fever was 8.7 months and 7.9 months for dengue hemorrhagic fever. Clinical signs and symptoms indicative of dengue were greatest among laboratory-positive cases and included fever, rash, thrombocytopenia, bleeding manifestations, and petechiae. The most common symptoms among patients who were laboratory-negative were fever, nasal congestion, cough, diarrhea, and vomiting. Using the 1997 WHO guidelines, nearly 50% of the laboratory-positive cases met the case definition for dengue fever, and 61 of these were further determined to meet the case definition for dengue hemorrhagic fever. In comparison, 15% of laboratory-negative cases met the case definition for dengue fever and less than 1% for dengue hemorrhagic fever. None of the laboratory-positive or laboratory-negative cases met the criteria for dengue shock syndrome.^

The History of Pathology in Texas

The History of Pathology in Texas is the study of the changes of disease in Texas from the frontier days to the 1990s. Marilyn Miller Baker wrote the book for the Texas Society of Pathologists. The book was published in 1996 with a forward by Vernie A. Stembridge, MD, the Ashbel Smith Professor and Chairman Emeritus of Pathology at the University of Texas Southwestern Medical Center at Dallas. The book covers the story of pathology from the "performance of crude autopsies" on the frontier through the emergence of bacteriology and immunology and beyond.