Regulation of the Human Parainfluenza Virus (hPIV3) Fusion Protein

Paramyxoviruses include a number of important human pathogens, including measles virus, mumps virus, and the human parainfluenza viruses (hPIV) 1-4, as well as several animal pathogens, such as Sendai virus, Nipah virus and Hendra virus. The creation of effective drugs and vaccines against this family of viruses would play an important role in decreasing the prevalence of these viruses and contributing to the health of both humans and animals worldwide. The purpose of this work was to determine how the fusion (F) protein is regulated with a focus on the heptad repeat B (HRB) region of the F protein located in the ectodomain, directly adjacent to the transmembrane domain. This region has been suggested to play important roles in the initiation of fusion (Gravel 2003) as well as in the formation of the final hairpin structure that drives fusion (Russell 2001). My investigation of the HRB region of the parainfluenza fusion (F) protein has been to characterize the structure of this domain in the pre-fusion form of the F protein in order to better understand the role it plays in fusion. An understanding of how F protein conformational changes are regulated may lead to the creation of more effective therapies against paramyxoviruses in general. A crystal structure obtained from the pre-fusion PIV5 F protein (Yin 2006) reveals that the HRB domain is in a triple stranded coiled coil conformation. However, in order to obtain the structure, a trimerization domain was used for structure stabilization. It is not known if the trimerization domain influenced the resulting crystal structure. My research has investigated the structure of the HRB region by creating mutations in both the pre-fusion hPIV3 F protein and peptides derived from the HRB region. Although much work still remains, preliminary results are consistent with the HRB region of the hPIV3 F protein forming a triple stranded coiled coil in the pre-fusion conformation

Perceptual-Motor Activity Resource Book

This paper gives a brief summary of the perceptual-motor theories of Kephart, Cratty, and Delacato, and discusses some of the research resulting from their theories. It also includes a resource book of perceptual-motor activities covering the areas of gross-motor skills, fine-motor skills, spatial awareness, body image, and laterality/ directionality. The activities have been arranged in chronological order according to skill level. The resource book is a compilation of materials from a perceptual-motor workshop held in the summer of 1978 by the University of Texas of the Permian Basin

Schools Respond to Risk Management Programs for Asbestos, Lead in Drinking Water and Radon

Based on a study of the three EPA-initiated, public school risk management programs noted in the title, the authors find that state agency involvement is an important factor in the success of such programs. They also find, e.g., that school districts are justifiably reluctant to comply with tentative program

Comparing bivalent and quadrivalent human papillomavirus vaccines: economic evaluation based on transmission model

Objectives To compare the effect and cost effectiveness of bivalent and quadrivalent human papillomavirus (HPV) vaccination, taking into account differences in licensure indications, protection against non-vaccine type disease, protection against disease related to HPV types 6 and 11, and reported long term immunogenicity

Postoperative Pain Trajectories in Cardiac Surgery Patients

Poorly controlled postoperative pain is a longstanding and costly problem in medicine. The purposes of this study were to characterize the acute pain trajectories over the first four postoperative days in 83 cardiac surgery patients with a mixed effects model of linear growth to determine whether statistically significant individual differences exist in these pain trajectories, and to compare the quality of measurement by trajectory with conventional pain measurement practices. The data conformed to a linear model that provided slope (rate of change) as a basis for comparing patients. Slopes varied significantly across patients, indicating that the direction and rate of change in pain during the first four days of recovery from surgery differed systematically across individuals. Of the 83 patients, 24 had decreasing pain after surgery, 24 had increasing pain, and the remaining 35 had approximately constant levels of pain over the four postoperative days

Perseverance with home-based upper limb practice after stroke: perspectives of stroke survivors and their significant others

Purpose: The aim of this study was to explore factors that influence stroke survivors’ ability to persevere with home-based upper limb practice. Methods: A qualitative descriptive study embedded within a theoretical framework was conducted. Data were collected through semi-structured focus group, dyadic, and individual interviews. The Theoretical Domains Framework and Capability, Opportunity, Motivation – Behaviour (COM-B) model guided data collection and directed content analysis. Findings: Participants were 31 adult stroke survivors with upper limb impairment, with 13 significant other/s, who were living at home in Queensland, Australia. Three central tenants aligned with the COM-B and six themes were identified. Stroke survivors’ capability to persevere was influenced by being physically able to practice and being able to understand, monitor and modify practice, their opportunity to persevere was influenced by accessing therapy and equipment required for practice and fitting practice into everyday life, and their motivation to persevere was influenced by having goals and experiencing meaningful outcomes and having support and being accountable. Conclusion: Persevering with practice is multifaceted for stroke survivors. All facets need to be addressed in the design of strategies to enhance stroke survivors’ ability to persevere and in turn, enhance their potential for continued upper limb recovery

Informed consent in palliative care clinical trials: challenging but possible

Obtaining informed consent is a key protection that should be afforded universally to people using health services and the basis around which any participation in clinical trials is built. Randomized controlled effectiveness studies are necessary to answer key questions in hospice and palliative care, in order to help systematically improve the quality of care. In order to be properly generalizable, such trials need to have broad inclusion criteria to reflect the population most likely to be affected by the condition. The inclusion of patients who are seriously ill, and therefore potentially vulnerable, requires careful exploration of ethical and legal principles that underpin informed consent. Specific challenges in obtaining informed consent for randomised clinical trials (RCTs) in clinically unstable populations such as hospice and palliative care include higher rates of people with impaired cognitive capacity as well as interventional studies in clinical situations which may present as a sudden change in condition. None of these challenges is unique to hospice and palliative care research, but the combination and frequency with which they are encountered require systematic and considered solutions. This article outlines five different ethically valid consent approaches and discusses their applicability to hospice and palliative care research trials. These include: consent by the patient (at the time of enrolment, in advance of the study, or delayed until after the study has commenced); a proxy (or legally authorised representative); or a consent waiver. Increased use of the less traditional modes of informed consent may lead to greater participation rates in hospice and palliative care trials, thereby improving the evidence base more rapidly in part by better reflecting the population served and hence improving generalizability

Estimating the public health impact of the effect of herpes simplex virus suppressive therapy on plasma HIV-1 viral load.

OBJECTIVE: Trials of herpes simplex virus (HSV) suppressive therapy among HSV-2/HIV-1-infected individuals have reported an impact on plasma HIV-1 viral loads (PVLs). Our aim was to estimate the population-level impact of suppressive therapy on female-to-male HIV-1 sexual transmission. DESIGN AND METHODS: By comparing prerandomization and postrandomization individual-level PVL data from the first two HSV suppressive therapy randomized controlled trials in sub-Saharan Africa, we estimated the effect of treatment on duration of asymptomatic infection and number of HIV-1 transmission events for each trial. RESULTS: Assuming that a reduction in PVL is accompanied by an increased duration of HIV-1 asymptomatic infection, 4-6 years of HSV suppressive therapy produce a 1-year increase in the duration of this stage. To avert one HIV-1 transmission requires 8.8 [95% confidence interval (CI), 5.9-14.9] and 11.4 (95% CI, 7.8-27.5) women to be treated from halfway through their HIV-1 asymptomatic period, using results from Burkina Faso and South African trials, respectively. Regardless of the timing of treatment initiation, 51.6 (95% CI, 30.4-137.0) and 66.5 (95% CI, 36.7-222.6) treatment-years are required to avert one HIV-1 infection. Distributions of set-point PVL values from sub-Saharan African populations suggest that unintended adverse consequences of therapy at the population level (i.e. increased HIV-1 transmission due to increased duration of infection) are unlikely to occur in these settings. CONCLUSION: HSV suppressive therapy may avert relatively few HIV-1 transmission events per person-year of treatment. Its use as a prevention intervention may be limited; however, further research into its effect on rate of CD4 cell count decline and the impact of higher dosing schedules is warranted

Defining the Indefinable: Descriptors of Aboriginal and Torres Strait Islander Peoples’ Cultures and their Links to Health and Wellbeing

This report was funded by the Lowitja Institute and is part of the development of Mayi Kuwayu: The National Study of Aboriginal and Torres Strait Islander Wellbeing; a national longitudinal study exploring the relationship between Aboriginal Torres Strait Islander wellbeing and culture. This review was conducted to explore what cultural factors are important to Aboriginal and Torres Strait Islander people and gain an understanding of how these factors relate to health and wellbeing. We examined the Australian literature as well as publications from countries that have experienced similar colonisation events; primarily Aotearoa (New Zealand), Canada and the United States. Our main findings from this synthesis determined six main domains used to describe culture for Aboriginal and Torres Strait Islander peoples. These domains were: Connection to Country; Cultural Beliefs and Knowledge; Language; Family, Kinship and Community; Expression and Cultural Continuity; and Self-determination and Leadership.The Lowitja Institute Aboriginal and Torres Strait Islander Health Cooperative Research Centre funded this review under project 16-SDH-05-03