The role of STAT1 in Chlamydia-induced type I interferon responses in oviduct epithelium

Indiana University-Purdue University Indianapolis (IUPUI)Progression of Chlamydia into upper reproductive tract epithelium and the induction of subsequent immune responses to infection are major contributors to Chlamydia-induced pathogenesis of the genital tract. We reported that C. muridarum infection of the oviduct epithelial cells (OEs) secrete IFN-β in a TLR3 dependent manner. However, we showed that the C. muridarum infected TLR3-deficient OEs were still able to secrete minimal amounts of IFN-β into the supernatants, which is suggestive that there are other signaling pathways that contribute to Chlamydia-induced IFN-β synthesis in these cells. Previous studies describing the activation of the JAK/STAT signaling pathway during Chlamydia infection of cervical epithelial cells proposes a putative role for STAT1 in the synthesis of type I IFNs during Chlamydia infection. The present study investigated the role of STAT1 in Chlamydia-induced IFN-β production in OEs. OEs were infected with Chlamydia muridarum and analyzed at 24 hours by RT-PCR and western blot to determine STAT1 expression. STAT (-/-) OEs were infected and IFN-β production measured by ELISA. Quantitative real-time PCR analyses were performed at 6 and 16 hour post-infection to elucidate the mechanisms involved in IFN-β production during infection. Fluorescent microscopy was used to observe changes in Chlamydia replication. STAT1 activation and expression were significantly increased in wild-type (WT) OEs upon infection. TLR3 (-/-) OEs showed diminished STAT1 protein activation and expression. Augmented STAT1 protein expression corresponded to STAT1 mRNA levels. ELISA analyses revealed significantly less IFN-β production in infected STAT1 (-/-) OEs compared to WT OEs. Quantitative real-time PCR data showed that gene expression of IFN-β and of type I IFN signaling components were significantly increased during late stage Chlamydia infection, dependent on STAT1. Temporal regulation and increases in expression of IFN-α subtypes during infection were STAT1-dependent. Our results implicate STAT1-mediated signaling as a contributor to the C. muridarum-induced synthesis of IFN-β and other type I IFNs in OEs. We previously described a major role for TLR3 in the early-stage Chlamydia-induced synthesis of IFN-β in OEs; the results from this study suggest a role for STAT1 in the synthesis of type I IFNs that occurs during early and late stages of infection

Triggered Electrical Stimulation Cueing to Address Hypofunctioning Peroneus Muscle in the Treatment of Chronic Ankle Instability: Two Repeated Single Case Designs

Background: Approximately two million ankle sprains occur in the United States annually. Lateral ankle sprains (LAS) account for 85% of all ankle sprains, 74% of those individuals report continued symptoms following the initial insult. Persistent pain and instability following ankle sprain is indicative of chronic ankle instability (CAI). There are many interventions to address hypofunctioning muscle including electrical stimulation (ES) and it is known that peripheral ES changes muscle behavior. The purpose of this pilot study was to investigate the effect of electrical stimulation of the peroneal muscles combined with 3 exercises for the treatment of CAI.Methods: Two participants with CAI were recruited for this repeated single case design. The Cumberland Ankle Instability Tool (CAIT), the modified Star Excursion Balance Test (mSEBT), and center of pressure (CoP) was measured. A single limb hop to stabilization protocol and single limb stance activities were combined with manual triggered electrical stimulation for six sessions.Results: Improvements in CAIT scores for both patients were observed. There was no statistically significant change in mSEBT scores. Center of Pressure measurement improvements varied between subjects. For subject 1, there was no significant change in CoP in eyes open and eyes closed conditions. For subject 2, there was a significant change in the anterior/posterior CoP data points in both conditions.Discussion: In individuals with CAI, the addition of electrical stimulation to a single limb stance and hop stabilization protocol for hypofunctioning peroneal muscles led to positive CAI outcomes as measured by improved CAIT scores and improved CoP measurement in one subject

Effect of Pitching Restrictions and Mound Distance on Youth Baseball Pitch Counts.

BACKGROUND: Studies have shown that higher pitch counts are directly related to a greater incidence of elbow and shoulder pain among youth baseball pitchers. PURPOSE/HYPOTHESIS: The purpose of this study was to examine the effect of different pitching restriction rules on the number of pitches thrown in youth baseball leagues. We hypothesized that more pitches would be thrown in leagues with inning restrictions versus leagues with pitch count restrictions as well as in leagues with a longer mound distance (from pitching mound to home plate). STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Pitch count data were collected for 2 consecutive years over a 10-week season from 3 different leagues of 9- to 12-year-old baseball players in a single city. The Eastern league had a pitch count restriction and 46-ft (14.02-m) mound distance. The Southeastern and South leagues\u27 pitching restrictions were based on innings per week. The Southeastern league had a 50-ft (15.24-m) mound distance, while the South league had a 46-ft mound distance. Comparisons of total seasonal pitches thrown were made of the 3 highest-volume pitchers on each team. League averages for each value were then compared utilizing analysis of variance with Bonferroni post hoc analysis. The number of pitchers in each league who threw \u3e600 pitches per season was compared using the chi-square test. RESULTS: No significant difference in seasonal pitch counts or innings pitched was noted between the Eastern and South leagues, which differed only in their pitching restrictions. The Southeastern league, with a longer mound distance, was found to have higher seasonal pitch counts per thrower (598 ± 195 pitches) than the South league (463 ± 198 pitches) for the 3 highest-volume throwers for each team ( CONCLUSION: There was no significant difference in seasonal pitch counts when the leagues in this study differed based on pitching restrictions. However, the league with a greater mound distance (Southeastern) had higher seasonal pitch counts for the highest-volume throwers. Pitching restrictions based on pitch counts, as opposed to innings, may be advisable

National Standards for Diabetes Self-Management Education

Diabetes self-management education (DSME) is a critical element of care for all people with diabetes and is necessary in order to improve patient outcomes. The National Standards for DSME are designed to define quality diabetes self-management education and to assist diabetes educators in a variety of settings to provide evidence-based education. Because of the dynamic nature of health care and diabetes-related research, these Standards are reviewed and revised approximately every 5 years by key organizations and federal agencies within the diabetes education community. A Task Force was jointly convened by the American Association of Diabetes Educators and the American Diabetes Association in the summer of 2006. Additional organizations that were represented included the American Dietetic Association, the Veteran's Health Administration, the Centers for Disease Control and Prevention, the Indian Health Service, and the American Pharmaceutical Association. Members of the Task Force included a person with diabetes; several health services researchers/behaviorists, registered nurses, and registered dietitians; and a pharmacist. The Task Force was charged with reviewing the current DSME standards for their appropriateness, relevance, and scientific basis. The Standards were then reviewed and revised based on the available evidence and expert consensus. The committee convened on 31 March 2006 and 9 September 2006, and the Standards were approved 25 March 2007

The Effect of Visitors on the Behavior of Zoo-Housed Western Lowland Gorillas (Gorilla gorilla gorilla)

Primates, especially apes, are popular with the public, often attracting large crowds. These crowds could cause behavioral change in captive primates, whether positive, neutral, or negative. We examined the impact of visitors on the behavior of six western lowland gorillas (Gorilla gorilla gorilla), observing the troop over 6 weeks during high season (4.5 hr/day, 35 days, May–July 2016). We used focal scan sampling to determine activity budget and enclosure usage, and focal continuous sampling to identify bouts of anxiety-related behavior (visitor-directed vigilance, self-scratching, and aggression). Both daily zoo-entry numbers (VGATE) and instantaneous crowds at the exhibit (VDENSITY) were measured. Overall, VGATE had little effect across behaviors. However, consistent with the more acute time frame of measurement, VDENSITY was a better predictor of behavior; at high crowd volumes, we observed significant group-level changes in activity budget (increased inactivity, increased locomotion, and decreased environment-related behaviors), increase in some anxiety-related behaviors, and decreased enclosure usage. Although contributing similar effects, it could not be determined if crowd numbers, composition, or noise most affected the troop, nor any chronic effects of exposure to large crowds. Nevertheless, our findings suggest that measures to minimize the impacts of large crowds at the exhibit would be beneficial. Furthermore, we highlight potential discrepancies between common methods for measuring visitor numbers: VGATE is less sensitive to detecting visitor effects on behavioral indices than VDENSITY. Future studies should appropriately match the biological time frame of welfare indicators and visitor measures used to ensure the reliability of findings

Participant Perspectives in an HIV Cure-Related Trial Conducted Exclusively in Women in the United States: Results from AIDS Clinical Trials Group 5366

Women remain underrepresented in HIV research. The AIDS Clinical Trials Group (ACTG) 5366 study was the first HIV cure-related trial conducted exclusively in women. Our multidisciplinary team integrated participant-centered reports into the ACTG 5366 protocol to elicit their perspectives. We nested mixed-methods surveys at the enrollment and final study visits to assess ACTG 5366 participants’ perceptions and experiences. Of 31 participants enrolled in the ACTG 5366, 29 study agreed to complete the entry questionnaire and 27 completed the exit survey. The majority of study participants were nonwhite. We identified societal and personal motivators for participation, understanding of risks and benefits, and minor misconceptions among some trial participants. Stigma was pervasive for several women who joined the study, and served as a motivator for study participation. Reimbursements to defray costs of study participation were reported to facilitate involvement in the trial by about one-third of participants. Almost all respondents reported positive experiences participating in the ACTG 5366 trial. The ACTG 5366 study showed that it is possible to recruit and retain women in HIV cure-related research and to embed participant-centered outcomes at strategic time points during the study. The findings could help in the design, implementation, recruitment, and retention of women in HIV cure-related research and highlight the value of assessing psychosocial factors in HIV cure-related research participation

Is radical innovation in architecture crucial to sustainability? Lessons from three Scottish contemporary buildings

Radical innovation is largely recognised as a medium for advancement, a source of growth for economies, and a trigger for progress in different economic sectors. Often, this type of innovation is identified with technological advancements, disruptive phenomena and the creation of new systems and dynamics. Yet, within the context of a changing world, in which principles of economic, environmental and social sustainability are largely adopted as common objectives, a reflection on the type of progress and the need for radical innovation is necessary with the aim of informing on their impacts and effectiveness. This work presents an analysis of a number of contemporary Scottish architectural designs, developed under the aegis of sustainability principles, and explores the types of sustainable innovations introduced and the results achieved by analyzing the type of design change that triggered specific sustainable results, demonstrating alternative innovation strategies, other than the radical one. This analysis provides a basis for discussion on the need for radical innovation in the context of sustainable architecture and explores the role of other types of innovation against the results achieved. This discussion could contribute to a better understanding of the current state of practice in architectural design, as well as in policy making in regard to the design and management of the future built environment