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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2010.08.026 Byline: Weipeng Mu, Robert J. Munroe, Anna K. Barker, John C. Schimenti Keywords: Mouse development; Embryonic stem cells; Cell differentiation; Preimplantation Abbreviations: ESC, embryonic stem cell; ICM, inner cell mass; RA, retinoic acid; MEF, mouse embryonic fibroblast; LIF, leukemia inhibitory factor Abstract: PDCD2 is a conserved eukaryotic protein implicated in cell cycle regulation by virtue of its interactions with HCFC1 and the NCOR1/SIN3A corepressor complex. Pdcd2 transcripts are enriched in ES cells and other somatic stem cells, and its ortholog is essential for hematopoietic stem cell maintenance in Drosophila. To characterize the physiological role(s) of mammalian PDCD2, we created a disruption allele in mice. Pdcd2.sup.-/- embryos underwent implantation but did not undergo further development. Inner cell masses (ICMs) from Pdcd2.sup.-/- blastocysts failed to outgrow in vitro. Furthermore, embryonic stem cells (ESCs) require PDCD2 as demonstrated by the inability to generate Pdcd2.sup.-/- ESCs in the absence of an ectopic transgene. Upon differentiation of ESCs by retinoic acid treatment or LIF deprivation, PDCD2 levels declined. In conjunction with prior studies, these results indicate that in vivo, PDCD2 is critical for blastomere and ESC maintenance by contributing to the regulation of genes in a manner essential to the undifferentiated state of these cells. Article History: Received 11 December 2009; Revised 6 August 2010; Accepted 24 August 2010

Venous leg ulcers are lower limb skin ulcers characterised by a cycle of healing and recurrence due to underlying chronic venous insufficiency. While compression improves healing outcomes, many ulcers do not heal. As a daily 300 mg oral dose of aspirin in conjunction with compression may improve healing outcomes, we investigated the effect of adjuvant aspirin on venous leg ulcer healing in participants already receiving compression. We conducted a prospective, randomised, double-blinded, placebo-controlled, clinical trial (known as ASPiVLU). Participants were recruited from six wound clinics in Australia. We screened 844 participants. Community-dwelling adult participants identified at six hospital outpatient clinics and clinically diagnosed with a venous leg ulcer present for 6+ weeks were eligible between April 13, 2015 to June 30, 2018. We randomised 40 participants (n = 19 aspirin, n = 21 placebo) and evaluated against the primary outcome. There were no dropouts. Ten serious adverse events in six participants were recorded. None were study related. The primary outcome measure was healing at 12 weeks based on blinded assessment. We found no difference in the number of ulcers healed at 12 weeks between the intervention and control groups. This study could not detect whether or not aspirin affected VLU healing speed. This is likely because we recruited fewer participants than expected due to the high number of people with venous leg ulcers in Australia who were already taking Aspirin; future research should investigate other adjuvant therapies or different study designs. • Daily 300 mg aspirin dose did not improve time to healing at 12 or 24 weeks or decrease recurrence rates when used as an adjuvant to compression. • Effect of aspirin on inflammation markers provided a unique analysis using ulceration characteristics and haematological factors. • Aspirin may affect inflammation processes implicated in venous leg ulcer recurrence through inducing rapid reductions in Interlukin-7. [ABSTRACT FROM AUTHOR]

As legal recreational marijuana use expands rapidly across the U.S., there is growing concern that this will lead to higher rates of use among college-aged young adults. Given the limited research addressing this issue, a longitudinal study was conducted to evaluate the effects of legalizing recreational use on the attitudes, intentions, and marijuana use behaviors of college students in two different legalization contexts, Washington State and Wisconsin. Survey data assessing marijuana attitudes, intentions, and use behavior were collected from 2011 to 2016 on a longitudinal cohort of 338 students at two large public universities in Washington and Wisconsin. Time series analyses were conducted to evaluate postlegalization changes in ever use, 28-day use, and mean attitude and intention-to-use scores in Washington state, using Wisconsin participants as the control group. Ever use, attitude, and intention-to-use scores did not change significantly more in Washington after legalization than in Wisconsin. However, among prior users, the proportion using in the last 28 days rose faster in Washington after legalization that it did in Wisconsin (p <.001). The findings suggest that legalization had the greatest effects on current marijuana users, who are surrounded by a climate that is increasingly supportive of its use. [ABSTRACT FROM AUTHOR]

• Same nurse and physician hand hygiene rates when measured by covert observation. • Better nurse than physician hospital-wide hand hygiene rates by overt observation. • No diurnal variation in hand hygiene, but decreased contact precaution use at night. Using an innovative, covert, in-room observer method to evaluate infection control practices for patients with Clostridioides difficile infection, we found no difference between physician and nursing hand hygiene compliance and contact precaution usage. There was also no diurnal variation in hand hygiene practices, but decreased contact precaution usage at night. Conversely, hospital-wide data from overt observations collected over the same time period showed significantly higher hand hygiene compliance among nurses than physicians. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to investigate risk factors for multidrug-resistant organism (MDRO) infection within patients from a tertiary care hospital in Northern India. This case-control study examined MDRO infection risk factors, including diet, health history, and medical device use. We administered a diet questionnaire to collect data on usual diet and collected data on other risk factors from chart review. All participants were inpatients identified through hospital microbiology reports. A total of 39 MDRO patient cases and 91 controls were included. Methods Descriptive statistics, univariate analysis, and multivariate logistic regression were performed to evaluate the association between risk factors and MDRO infection. Results All cases had gram-negative MDRO infections. Univariate analyses found length of hospital stay, connective tissue disease, hospitalization in the last 12 months, hospitalization of a family member, in-hospital antibiotic use, antibiotic use in the last 12 months, and feeding tube, central venous line, and urinary catheter use to be significantly different between cases and controls. Logistic regression showed a >3-fold increase in the odds of infection with antibiotic use in the last 12 months (odds ratio [OR], 3.30; 95% confidence interval [CI], 1.22-8.91) and urinary catheter use (OR, 3.63; 95% CI, 1.14-11.58). Differences in dietary preferences and fruit, vegetable, and fiber consumption were not significantly associated with infection. Conclusions Antibiotic use is a major driver of MDRO infections. Our findings suggest that interventions optimizing antibiotic stewardship and reducing device use should be a priority to prevent MDRO infections. [ABSTRACT FROM AUTHOR]

Background Staphylococcus aureus ( S. aureus ) is an organism of great public health importance, causing 20,000 deaths annually. Decolonization of patients with S. aureus may prevent infections, yet current options are limited to antimicrobials that promote antibiotic resistance and can cause adverse side effects. Probiotics have potential to reduce colonization of pathogenic bacteria, representing a promising alternative for S. aureus decolonization, but thus far lack rigorous evaluation. Methods Potential subjects were recruited from inpatient and outpatient settings within a VA medical center and screened for S. aureus gastrointestinal (GI) or extra-GI colonization using swabs at multiple body sites. Positive, eligible, consenting participants were stratified by colonization site and randomized in a 1:1 ratio to 4-weeks of daily placebo or Lactobacillus rhamnosus ( L. rhamnosus ) HN001 probiotic treatment. Blood and stool samples, and treatment adherence reports were collected from each subject throughout the study, along with a final set of swabs at study completion to detect S. aureus carriage. The outcomes of this study are GI or extra-GI carriage by S. aureus at the end of 4 weeks of therapy, change in phagocytic activity of polymorphonuclear cells from pre-intervention to post-intervention, and symptomatic S. aureus infection at any site during the study period. Conclusion 114 participants have been recruited for this study. Analysis of outcomes is underway. This is the first clinical trial to examine the efficacy of L. rhamnosus HN001 for decolonization of S. aureus , and investigates the mechanism by which L. rhamnosus HN001 mediates its effect on S. aureus colonization. ClinicalTrials.gov Identifier NCT01321606 [ABSTRACT FROM AUTHOR]

Patients with Clostridium difficile infection (CDI) are placed in contact precautions. We surveyed 31 visitors of CDI patients to understand their compliance, knowledge, and perceptions of contact precautions. Although most visitors knew where to find the required personal protective equipment, only 42% were fully compliant with gown and gloves. Family members accounted for 90% of visitors, and roughly half of the reasons given for not gowning were related to a lack of perceived risk for family members. Nursing staff are fundamental sources of personal protective equipment (PPE) information for visitors; however, we found variation in staff communication regarding need for visitor PPE use. [ABSTRACT FROM AUTHOR]

Background Clostridium difficile is a pathogen of rapidly increasing public health importance. An estimated quarter of a million Clostridium difficile infections (CDI) occur in the United States annually, at a resultant cost of 14,000 deaths and 1 billion dollars. Clostridium difficile related deaths have risen 400% over the last decade, and current standard antibiotic treatments are only 75 to 85% successful. Besides increasing the risk of antibiotic resistance and side effects, these treatments are very expensive. The most vulnerable population for Clostridium difficile is older adults, who make up approximately half of the cases, but account for 90% of the related deaths. Probiotics may have potential as adjunctive therapeutic agents for CDIs, however, current data is limited. Methods This pilot study is a single-site, randomized, placebo-controlled, double-blind, phase two clinical trial. The trial primarily evaluates the effect of four weeks of probiotic therapy in addition to standard of care on Clostridium difficile diarrhea duration and recurrence. Secondary outcomes include effect on fecal cytokines, fecal lactoferrin, and Clostridium difficile toxin density in stool, as well as patient functional status. Discussion This pilot study will determine the feasibility and effect size to conduct larger randomized controlled trials of probiotic interventions in patients with CDI, to determine the impact of probiotics on the symptoms of CDI. ClinicalTrials.gov Identifier: NCT01680874 [ABSTRACT FROM AUTHOR]

Objectives To investigate the effect of Pilates on balance and falls in older adults, and whether programs tested in prior studies met best-practice recommendations for exercise to prevent falls. Data Sources MEDLINE, SPORTDiscus, CINAHL, PubMed, Physiotherapy Evidence Database, and The Cochrane Library were searched from earliest record to July 2014. Study Selection Randomized and controlled clinical trials evaluating the effect of Pilates on balance and/or falls in older adults. Data Extraction Two reviewers independently extracted demographic, intervention, and outcome data. Six studies were included in this review. Data Synthesis High-quality studies in this area are lacking. When compared with nonactive control groups, Pilates was shown to improve balance (standardized mean difference [SMD]=.84; 95% confidence interval [CI], .44–1.23; 6 studies) and reduce the number of falls (SMD=−2.03; 95% CI, −2.66 to −1.40; 1 study). Three studies provided sufficient detail to enable assessment of compliance with the recommendation of exercises providing a moderate or high challenge to balance. In these studies, 2% to 36% of exercises were assessed as providing a moderate or high challenge to balance. All studies provided ≥2 hours of exercise per week, and 1 study provided >50 hours of exercise during the study period. Conclusions The evidence suggests Pilates can improve balance, an important risk factor for falls in older adults. However, there is limited data on the impact of Pilates on falls. Effects may have been overestimated because of the low methodological quality of studies. Best-practice recommendations were rarely applied in prior studies, indicating greater effects may have been achieved if recommendations were incorporated. [ABSTRACT FROM AUTHOR]

Person-centered care is often equated with quality nursing home care. At the same time, quality mobility care contributes to residents' independence and quality of life. Realist evaluation and mixed methods were employed to evaluate the feasibility of a multi-faceted training intervention focused on personcentered mobility care. Staff and ambulatory residents of a ninety bed Australian nursing home with 3 units--one dementia-specific--participated. The intervention consisted of training sessions, weekly mobility care huddles and reflective practice sessions with individual staff. This study demonstrated the feasibility of an intervention aiming to improve person-centered mobility care in nursing homes; it was practical and well accepted. Study methods and outcome measures were suitable. Outcome measures demonstrated capacity to determine the effectiveness of the intervention in a larger randomized controlled trial. Focus groups provided insights regarding the context and mechanisms of change. Future research is recommended to evaluate intervention effectiveness and sustainability. [ABSTRACT FROM AUTHOR]

The prevalence of Clostridium difficile spores was assessed in 48 observations of infected inpatients. Participants were randomized to hand hygiene with either alcohol-based handrub or soap and water. C difficile was recovered in 14.6% of pre-hand hygiene observations. It was still present on 5 of these 7 participants after hand hygiene (3/3 using alcohol-based handrub; 2/4 using soap and water). [ABSTRACT FROM AUTHOR]

Objective To investigate the effectiveness of aquatic exercise in the management of musculoskeletal conditions. Data Sources A systematic review was conducted using Ovid MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, and The Cochrane Central Register of Controlled Trials from earliest record to May 2013. Study Selection We searched for randomized controlled trials (RCTs) and quasi-RCTs evaluating aquatic exercise for adults with musculoskeletal conditions compared with no exercise or land-based exercise. Outcomes of interest were pain, physical function, and quality of life. The electronic search identified 1199 potential studies. Of these, 1136 studies were excluded based on title and abstract. A further 36 studies were excluded after full text review, and the remaining 26 studies were included in this review. Data Extraction Two reviewers independently extracted demographic data and intervention characteristics from included trials. Outcome data, including mean scores and SDs, were also extracted. Data Synthesis The Physiotherapy Evidence Database (PEDro) Scale identified 20 studies with high methodologic quality (PEDro score ≥6). Compared with no exercise, aquatic exercise achieved moderate improvements in pain (standardized mean difference [SMD]=−.37; 95% confidence interval [CI], −.56 to −.18), physical function (SMD=.32; 95% CI, .13–.51), and quality of life (SMD=.39; 95% CI, .06–.73). No significant differences were observed between the effects of aquatic and land-based exercise on pain (SMD=−.11; 95% CI, −.27 to .04), physical function (SMD=−.03; 95% CI, −.19 to .12), or quality of life (SMD=−.10; 95% CI, −.29 to .09). Conclusions The evidence suggests that aquatic exercise has moderate beneficial effects on pain, physical function, and quality of life in adults with musculoskeletal conditions. These benefits appear comparable across conditions and with those achieved with land-based exercise. Further research is needed to understand the characteristics of aquatic exercise programs that provide the most benefit. [ABSTRACT FROM AUTHOR]

Abstract: Background: Chronic heart failure (CHF) accounts for significant morbidity, mortality and health expenditure. Furthermore, patients with CHF are often on numerous pharmacological agents for their comorbidities. The objective of this study was to determine whether a pharmacist directed home medication review intervention had positive effects on CHF patient outcomes. Methods: A total of 120 patients hospitalised for CHF were randomised to receive a pharmacist directed post-discharge home medication review (n=64, 53.3%) or standard care (n=56, 46.7%). Participants were followed for 6months. Primary outcomes were death, CHF hospitalisation and length of hospital stay. Results: There were no between group differences in mortality (hazard ratio=1.41, 0.50 to 3.97; P=0.514) or CHF hospitalizations (incidence rate ratio [IRR]=1.74 95% CI: 0.85–3.60 P=0.131) over the 6month follow-up period. Days of hospital stay for CHF exacerbations in the 6month follow-up were significantly greater in the intervention group (IRR=2.34 95% CI: 1.80–3.05 P=0.000). Conclusions: Post-discharge pharmacy directed home medication review appeared to have no effect on mortality and health care utilisation above that achieved with standard care. The post-acute management of CHF must be a collaborative multi-disciplinary effort by the health care team as it is the additive effect of interventions that are most effective. [Copyright &y& Elsevier]

Abstract: Barker AL, Nitz JC, Low Choy NL, Haines TP. Clinimetric evaluation of the Physical Mobility Scale supports clinicians and researchers in residential aged care. Objective: To investigate the interrater agreement and the internal construct validity of the Physical Mobility Scale, a tool routinely used to assess mobility of people living in residential aged care. Design: Prospective, multicenter, external validation study. Setting: Nine residential aged care facilities in Australia. Participants: Residents (N=186). Phase 1 cohort (99 residents; mean age, 85.22±5.1y); phase 2 cohort (87 residents; mean age, 81.59±10.69y). Interventions: Not applicable. Main Outcome Measures: Kappa statistics, minimal detectable change (MDC90) scores, and Bland-Altman plots were used to assess interrater agreement. Scale unidimensionality, item hierarchy, and person separation were examined with Rasch analysis for both cohorts. Results: Agreement between raters on 6 of the 9 Physical Mobility Scale items was high (κ>.60). The MDC90 value was 4.39 points, and no systematic differences in scores between raters were found. The Physical Mobility Scale showed a unidimensional structure demonstrated by fit to the Rasch model in both cohorts (phase 1: χ2=23.90, P=.16, person separation index=0.96; phase 2: χ2=22.00, P=.23, person separation index=0.96). Standing balance was the most difficult item in both cohorts (phase 1: logit=2.48, SE, 0.16; phase 2: logit=2.53, SE, 0.15). The person-item threshold map indicated no floor or ceiling effects in either cohort. Conclusions: The Physical Mobility Scale demonstrated good interrater agreement and internal construct validity with good fit to the Rasch model in both cohorts. The comparative results across the 2 cohorts indicate generality of the findings. The Physical Mobility Scale total raw scores can be converted to Rasch transformed scores, providing an interval measure of mobility. The Physical Mobility Scale may be suited to a range of clinical and research applications in residential aged care. [Copyright &y& Elsevier]

Contact precautions are complex behavioral interventions. To better understand barriers to compliance, we conducted a prospective study that compared the time burden for health care workers caring for contact precautions patients versus other patients. We found that nurses spent significantly more time in the rooms of contact precautions patients. There was no significant change in physician timing. Future studies need to evaluate workflow changes so that barriers to contact precaution implementation can be fully understood and addressed. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson's disease prevalence has been associated with rurality and pesticide use in studies throughout the world. Here, Parkinson's disease (PD) medication usage was used to estimate prevalence in 79 urban and rural localities in Victoria, Australia (5.3 million people).Methods: An ecological study design was used to determine whether PD medication usage, as a reporter of PD diagnosis, differed between 79 regions in Victoria, and whether variance in PD prevalence was associated with population demographics using multiple regression. Cluster formation probability was calculated using Monte Carlo modelling. The association between agricultural production and PD prevalence was conducted with Bonferroni-adjusted Mann-Whitney-U tests.Results: PD prevalence in Victoria was estimated to be 0.85%, which was greater in rural (1.02%) compared to urban (0.80%) locations; a difference that was abolished when corrected for demographic variables. Four of the highest prevalent regions (regardless of covariate adjustment) were clustered in northwest Victoria; a formation that was unlikely to be due to chance (P = 0.00095). These regions had increased production of pulse crops.Conclusions: PD prevalence was not associated with rurality, but associated with areas of pulse production. Pulses are plants of the fabaceae family, where many of these species secrete the PD toxin, rotenone, as a natural pesticide, which may underlie increased risk. This study is limited by the data collection method, where people who do not take PD medication for their disease, or take PD-associated medication for other diseases, may impact the estimated prevalence. [ABSTRACT FROM AUTHOR]

Objective: Patient narratives, or stories, are an effective means of educating patients because they increase personal relevance and may reduce counter-arguing. However, such stories must seamlessly combine evidenced-based health information while being true to real patient experiences. The purpose of this paper is to describe the process of developing an educational intervention using African-American patients’ success stories controlling hypertension. Methods: We identified a process to address stories development challenges. Results: (1) To help identify story tellers, we conducted a literature review and subsequently streamlined the process of storyteller identification through screening and telephone interviews. (2) To better elicit stories, we consulted with experts in storytelling and incorporated principles from theater. (3) To select stories, we used intervention mapping to map the intervention to theory and key clinical concepts, and also engaged members of the target community to ensure scientific criteria and maintain authenticity. Conclusion: Using personal narratives as intervention requires weaving together science, theory and clinically sound content, while still being true to the art of storytelling. Through a careful process of identifying storytellers and story selection and drawing upon theater arts, creating stories for intervention can be streamlined while meeting the goals of authenticity and scientific soundness. [Copyright &y& Elsevier]

To examine the (1) cohort of individuals living at home with Home Care Packages (HCPs) in 2016, (2) their access to other aged care services after HCP commencement, and (3) their hospital and ambulance service utilization. A cross-sectional study was conducted using integrated aged care and health care data contained within the National Historical Cohort of the Registry of Senior Australians. This study included people who accessed HCP between January 1, 2016 and December 31, 2016. The access to permanent residential aged care, transition care, respite care, hospital and ambulance services among Australian HCP recipients ≥65 years old in 2016 was evaluated. Descriptive statistics were employed. In 2016, 84,681 individuals received HCPs, of which 68.4% (n = 57,942) accessed HCP levels 1‒2, 26.0% (n = 22,057) accessed HCP levels 3‒4, and 5.5% (n = 4682) accessed both care levels within the year. Of the individuals receiving HCP, 34.0% (n = 27,787) started services that year and 16.7% (n = 14,117) moved to permanent residential aged care, 18.4% (n = 15,592) used respite care and 5.8% (n = 4937) used transition care that year. Emergency department (ED) presentations [43.6%, 95% confidence interval (CI) 43.3‒44.0] were the most common hospital encounters, followed by inpatient hospitalizations for any reason (43.3%, 95% CI 42.9‒43.7), and unplanned hospitalizations (38%, 95% CI 37.6‒38.3). Forty-four percent (44.5%, 95% CI 43.9‒45.0) of individuals utilized ambulance services. ED presentations, hospitalization for any reason, and unplanned hospitalizations were more common in individuals receiving HCP levels 3‒4 compared with those accessing HCP levels 1‒2. HCP recipients in Australia have frequent hospitalizations, including ED presentations. In addition, almost 1 in 5 access respite care and 16.7% transition to permanent residential care each year. As the population accessing HCP is increasing, adequate support for these individuals to live well at home and avoid health events that lead to hospitalizations are necessary. [ABSTRACT FROM AUTHOR]

We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control. [ABSTRACT FROM AUTHOR]