Canonical Wnt signaling in megakaryocytes regulates proplatelet formation.

Wnt signaling is involved in numerous aspects of vertebrate development and homeostasis, including the formation and function of blood cells. Here, we show that canonical and noncanonical Wnt signaling pathways are present and functional in megakaryocytes (MKs), with several Wnt effectors displaying MK-restricted expression. Using the CHRF288-11 cell line as a model for human MKs, the canonical Wnt3a signal was found to induce a time and dose-dependent increase in ß-catenin expression. ß-catenin accumulation was inhibited by the canonical antagonist dickkopf-1 (DKK1) and by the noncanonical agonist Wnt5a. Whole genome expression analysis demonstrated that Wnt3a and Wnt5a regulated distinct patterns of gene expression in MKs, and revealed a further interplay between canonical and noncanonical Wnt pathways. Fetal liver cells derived from low-density-lipoprotein receptor-related protein 6-deficient mice (LRP6(-/-)), generated dramatically reduced numbers of MKs in culture of lower ploidy (2N and 4N) than wild-type controls, implicating LRP6-dependent Wnt signaling in MK proliferation and maturation. Finally, in wild-type mature murine fetal liver-derived MKs, Wnt3a potently induced proplatelet formation, an effect that could be completely abrogated by DKK1. These data identify novel extrinsic regulators of proplatelet formation, and reveal a profound role for Wnt signaling in platelet production.

Person-centred quality indicators are associated with unplanned care use following hospital discharge.

OBJECTIVE: Performance indicators are used to evaluate the quality of healthcare services. The majority of these, however, are derived solely from administrative data and rarely incorporate feedback from patients who receive services. Recently, our research team developed person-centred quality indicators (PC-QIs), which were co-created with patients. It is unknown whether these PC-QIs are associated with unplanned healthcare use following discharge from hospital. DESIGN: A retrospective, cross-sectional study. METHODS: Survey responses were obtained from April 2014 to September 2020 using the Canadian Patient Experiences Survey - Inpatient Care instrument. Logistic regression models were used to predict the link between eight PC-QIs and two outcomes; unplanned readmissions within 30 days and emergency department visits within 7 days. RESULTS: A total of 114 129 surveys were included for analysis. 6.0% of respondents (n=6854) were readmitted within 30 days, and 9.9% (n=11 287) visited an emergency department within 7 days of their index discharge. In adjusted models, 'top box' responses for communication between patients and physicians (adjusted OR (aOR)=0.82, 95% CI: 0.77 to 0.88), receiving information about taking medication (aOR=0.86, 95% CI: 0.80 to 0.92) and transition planning at hospital discharge (aOR=0.79, 95% CI: 0.73 to 0.85) were associated with lower odds of emergency department visit.Likewise, 'top box' responses for overall experience (aOR=0.87, 95% CI: 0.82 to 0.93), communication between patients and physicians (aOR=0.73, 95% CI: 0.67 to 0.80) and receiving information about taking medication (aOR=0.90, 95% CI: 0.83 to 0.98), were associated with lower odds of readmission. CONCLUSIONS: This study demonstrates that patient reports of their in-hospital experiences may have value in predicting future healthcare use. In developing the PC-QIs, patients indicated which elements of their hospital care matter most to them, and our results show agreement between subjective and objective measures of care quality. Future research may explore how current readmission prediction models may be augmented by person-reported experiences.

An Automated System for Physician Trainee Procedure Logging via Electronic Health Records.

Importance: Procedural proficiency is a core competency for graduate medical education; however, procedural reporting often relies on manual workflows that are duplicative and generate data whose validity and accuracy are difficult to assess. Failure to accurately gather these data can impede learner progression, delay procedures, and negatively impact patient safety. Objective: To examine accuracy and procedure logging completeness of a system that extracts procedural data from an electronic health record system and uploads these data securely to an application used by many residency programs for accreditation. Design, Setting, and Participants: This quality improvement study of all emergency medicine resident physicians at University of California, San Diego Health was performed from May 23, 2023, to June 25, 2023. Exposures: Automated system for procedure data extraction and upload to a residency management software application. Main Outcomes and Measures: The number of procedures captured by the automated system when running silently compared with manually logged procedures in the same timeframe, as well as accuracy of the data upload. Results: Forty-seven residents participated in the initial silent assessment of the extraction component of the system. During a 1-year period (May 23, 2022, to May 7, 2023), 4291 procedures were manually logged by residents, compared with 7617 procedures captured by the automated system during the same period, representing a 78% increase. During assessment of the upload component of the system (May 8, 2023, to June 25, 2023), a total of 1353 procedures and patient encounters were evaluated, with the system operating with a sensitivity of 97.4%, specificity of 100%, and overall accuracy of 99.5%. Conclusions and Relevance: In this quality improvement study of emergency medicine resident physicians, an automated system demonstrated that reliance on self-reported procedure logging resulted in significant procedural underreporting compared with the use of data obtained at the point of performance. Additionally, this system afforded a degree of reliability and validity heretofore absent from the usual after-the-fact procedure logging workflows while using a novel application programming interface-based approach. To our knowledge, this system constitutes the first generalizable implementation of an automated solution to a problem that has existed in graduate medical education for decades.

Variation in parental experiences with their child's hospitalization over the COVID-19 pandemic.

BACKGROUND: Hospitals and healthcare workers have been greatly impacted by the COVID-19 pandemic. The potential impacts upon the patient experience have been less documented, particularly in the pediatric setting. Our aim was to examine how parental experiences with their child's hospitalization varied during the COVID-19 pandemic at two children's hospitals in Alberta, Canada. METHODS: A random sample of parents were surveyed within six weeks of their child's discharge from Alberta's two children's hospitals. Surveys were administered using the Alberta Pediatric Inpatient Experiences Survey (APIES) - a validated instrument used to assess parental experiences during their child's hospitalization. Surveys were linked with administrative inpatient records. Three cohorts were created based on hospital discharge date: Pre-COVID (Pre: April 2019 to March 2020), COVID year one (C1: April 2020 to March 2021), and COVID year two (C2: April 2021 to March 2022). We examined 48 survey questions, including four overall rating scales. Survey responses were Likert scales. These were transformed to normalized scores from 0 (worst) to 100 (best). Differences between cohorts were assessed using ANOVA and the post-hoc Tukey test. RESULTS: A total of 3,611 surveys (1,314 Pre; 997 C1; 1,300 C2) were completed over the three-year period. Five questions showed differences between the Pre and C1 periods, six showed differences between Pre and C2, and 13 showed differences between C1 and C2. Among these questions, scores pre-COVID were lower than COVID year one, while results in COVID year two were lower than pre-COVID and COVID year one. Thirty-one survey questions showed no statistical differences between the three time periods. For the overall ratings, only hospital rating showed a difference in any of the periods (91.4 C1 vs. 90.2 C2). Overall ratings of doctors, nurses, and recommendation of the hospital to others showed no differences. CONCLUSION: This study showed that the experiences of parents during the first year of the COVID-19 pandemic were mildly better or comparable to historical results. This changed over the following year, where lower scores were reported on 13 questions.

Income inequality and daily use of cannabis, cigarettes, and e-cigarettes among Canadian secondary school students: Results from COMPASS 2018-19.

INTRODUCTION: Cannabis, cigarette, and e-cigarette use among Canadian adolescents is a major public health concern. Income inequality has been associated with adverse mental health among youth and may contribute to the risk of frequent cannabis, cigarette, and e-cigarette use. We tested the association between income inequality and the risk of daily cannabis, cigarette, and e-cigarette use among Canadian secondary school students. METHODS: We used individual-level survey data from Year 6 (2018/19) of Cannabis, Obesity, Mental health, Physical activity, Alcohol use, Smoking, and Sedentary Behavior (COMPASS) and area-level data from the 2016 Canadian Census. Three-level logistic models were used to assess the relationship between income inequality and adolescent daily and current cannabis use, cigarette smoking, and e-cigarette use. RESULTS: The analytic sample included 74,501 students aged 12-19. Students were most likely to report being male (50.4%), white (69.1%), and having weekly spending money over $100 (23.5%). We found that a standard deviation unit increase in Gini coefficient was significantly associated with increased likelihood of daily cannabis use (OR=1.25, 95% CI = 1.01-1.54) when adjusting for relevant covariates. We found no significant relationship between income inequality and daily smoking. While Gini was not significantly associated with daily e-cigarette use, we observed a significant interaction between Gini and gender (OR=0.87, 95% CI= 0.80-0.94), indicating that increased income inequality was associated with higher risk of reporting daily e-cigarette use among females only. DISCUSSION: An association between income inequality and the likelihood of reporting daily cannabis use across all students and daily e-cigarette use in females were observed. Schools in higher income inequality areas may benefit from targeted prevention and harm reduction programs. Results emphasize the need for upstream discussion on policies that can mitigate the potential effects income inequality.

Canonical Wnt signaling negatively regulates platelet function.

Wnts regulate important intracellular signaling events, and dysregulation of the Wnt pathway has been linked to human disease. Here, we uncover numerous Wnt canonical effectors in human platelets where Wnts, their receptors, and downstream signaling components have not been previously described. We demonstrate that the Wnt3a ligand inhibits platelet adhesion, activation, dense granule secretion, and aggregation. Wnt3a also altered platelet shape change and inhibited the activation of the small GTPase RhoA. In addition, we found the Wnt-beta-catenin signaling pathway to be functional in platelets. Finally, disruption of the Wnt Frizzled 6 receptor in the mouse resulted in a hyperactivatory platelet phenotype and a reduced sensitivity to Wnt3a. Taken together our studies reveal a novel functional role for Wnt signaling in regulating anucleate platelet function and may provide a tractable target for future antiplatelet therapy.

Drivers of paediatric inpatient experience: retrospective analysis of casemix factors for the Alberta Paediatric Inpatient Experience Survey in Alberta, Canada.

OBJECTIVE: In Alberta, the Alberta Paediatric Inpatient Experience Survey (APIES) is used as a proxy-reported measure of paediatric experience. To our knowledge, the influence of casemix factors on patient experience as measured by paediatric patient experience surveys have not been reported within Canadian paediatric samples. In this paper, we sought to determine the patient and respondent factors associated with paediatric inpatient experiences in Alberta, Canada. DESIGN: Retrospective analysis of patient experience survey data. SETTING: Inpatiet acute care hospitals in Alberta, Canada. INTERVENTION AND MAIN OUTCOME MEASURES: Retrospective analyses were conducted using APIES surveys linked with eligible inpatient records (n=6262). Descriptive statistics were reported. χ2 tests were performed to assess distribution of casemix between general and paediatric hospitals. Logistic regression was performed with overall hospital experience as the dependent variable with casemix and hospital variables as independent variables. RESULTS: Casemix characteristics were unevenly distributed between general and paediatric hospitals. Compared with reference categories, older respondents, healthier patients and treatment at paediatric facilities had increased odds of providing most-positive ratings. Increased respondent education was associated with decreased odds of providing most-positive ratings. Likelihood-ratio tests showed that most casemix variables improved model fit, except for respondent relationship to the patient. CONCLUSIONS: To improve reports of paediatric inpatient experience, administrators and providers require reliable and comparable measurement. Both the Child Hospital Consumer Assessment of Healthcare Providers and Systems and other measures of patient and family experience need to consider patient and respondent characteristics when interpreting results. Considered with other research from patient experience in Alberta, we discuss future directions and quality improvement implications.

Adult Experiences with Hospitalization in Alberta, Canada During the COVID-19 Pandemic: A Comparative Cross-Sectional Study.

Little is known about the experiences of those hospitalized during the COVID-19 pandemic in Canada. Our aims were to (a) report on the experiences, (b) compare with historical results, and (c) assess for potential monthly differences of patients hospitalized in the early months of the COVID-19 across Alberta. A random sample of adults was surveyed within 6 weeks of discharge from 93 hospitals, using a modified version of the Canadian Patient Experiences Survey - Inpatient Care (CPES-IC). Discharges from April to September 2020 comprised the "during COVID-19 pandemic" cohort, while April to September 2019 formed the historical one. Results were reported as percent in "top box", indicative of the most positive answer choice. Odds of reporting a "top box" response were calculated while controlling for demographic and clinical features. In total, 23,412 surveys (11,344 during COVID-19, 12,068 historical) were obtained. Those hospitalized during COVID-19 had higher odds of "top box" ratings on 17 of 39 questions examined, and lower odds on 2 questions (information about the admission process, inclusion of family/friends in care decisions). The remaining 20 questions showed no difference between the 2 cohorts. Our results indicate that respondents hospitalized during the early months of the pandemic had experiences that were largely better or comparable to pre-pandemic. This speaks to the dedication and resilience of staff who provided care during challenging circumstances. Our findings may assist in mitigating fears among those who are hesitant to seek medical care during future pandemics or public health emergencies, including subsequent waves of COVID-19.

Family-Rated Pediatric Health Status Is Associated With Unplanned Health Services Use.

OBJECTIVE: Self-rated health is a common self-reported health measure associated with morbidity, mortality, and health care use. The objective was to investigate the association of family-rated health status (FRH) in pediatric care with administrative indicators, patient and respondent features, and unplanned health services use. PATIENTS AND METHODS: Data were taken from Child-Hospital Consumer Assessment of Healthcare Providers and Systems surveys collected between 2015 and 2019 in Alberta, Canada and linked with administrative health records. Three analyses were performed: correlation to assess association between administrative indicators of health status and FRH, logistic regression to assess respondent and patient characteristics associated with FRH, and automated logistic regression to assess the association between FRH and unplanned health services use within 90 days of discharge. RESULTS: A total of 6236 linked surveys were analyzed. FRH had small but significant associations with administrative indicators. Models of FRH had better fit with patient and respondent features. Respondent relationship to child, child age, previous hospitalizations, and number of comorbidities were significantly associated with ratings of FRH. Automated models of unplanned services use included FRH as a feature, and poor ratings of health were associated with increased odds of emergency department visits (adjusted odds ratio: 2.15, 95% confidence interval: 1.62-2.85) and readmission (adjusted odds ratio: 2.48, 95% confidence interval: 1.62-2.85). CONCLUSION: FRH is a simple, single-item global rating of health for pediatric populations that provides accessible and useful information about pediatric health care needs. The results of this article serve as a reminder that family members are valuable sources of information that can improve care and potentially prevent unplanned health services use.

How to analyze and link patient experience surveys with administrative data to drive health service improvement - examples from Alberta, Canada.

The ability of hospitals and health systems to learn from those who use its services (i.e., patients and families) is crucial for quality improvement and the delivery of high-quality patient-centered care. To this end, many hospitals and health systems regularly collect survey data from patients and their families, and are engaged in activities to publicly report the results. Despite this, there has been limited research into the experiences of patients and families, and how to improve them. Since 2015, our research team has conducted a variety of studies which have explored patient experience survey data, in isolation, and in linkages with routinely-captured administrative data sets across Alberta; a Canadian province of 4.4 million residents. Via secondary analyses, these studies have shed light upon the drivers of inpatient experience, the specific aspects of care which are most correlated with one's overall experiences, and the association of elements of the patient experience with other measures, such as patient safety indicators and unplanned hospital readmissions. The aim of this paper is to provide an overview of the methods we have used, including further details about the data sets and linkage protocol. The main findings from these papers have been presented for readers and those who wish to conduct their own work in this area.

The relationship between voting restrictions and COVID-19 case and mortality rates between US counties.

BACKGROUND: Since the 2010 election, the number of laws in the U.S. that create barriers to voting has increased dramatically. These laws may have spillover effects on population health by creating a disconnect between voter preferences and political representation, thereby limiting protective public health policies and funding. We examine whether voting restrictions are associated with county-level COVID-19 case and mortality rates. METHODS: To obtain information on restricted access to voting, we used the Cost of Voting Index (COVI), a state-level measure of barriers to voting during a U.S. election from 1996 to 2016. COVID-19 case and mortality rates were obtained from the New York Times' GitHub database (a compilation from multiple academic sources). Multilevel modeling was used to determine whether restrictive voting laws were associated with county-level COVID-19 case and mortality rates after controlling for county-level characteristics from the County Health Rankings. We tested whether associations were heterogeneous across racial and socioeconomic groups. RESULTS: A significant association was observed between increasing voting restrictions and COVID-19 case (ß = 580.5, 95% CI = 3.9, 1157.2) and mortality rates (ß = 16.5, 95% CI = 0.33,32.6) when confounders were included. CONCLUSIONS: Restrictive voting laws were associated with higher COVID-19 case and mortality rates.

Genome Sequences of Microbacterium foliorum Bacteriophages StrawberryJamm, Quammi, Teehee, and Casend.

Four microbacteriophages infecting the host Microbacterium foliorum were isolated at Gonzaga University as part of the SEA-PHAGES program. Phages Teehee, StrawberryJamm, Quammi, and Casend are in the EG cluster, with average genome sizes of 62,263 bp and GC contents of 67.2%, with other interesting characteristics.

Sex Differences in the Care Experiences of Patients Hospitalized Due to Ischemic Heart Disease in Alberta, Canada.

BACKGROUND: Women with heart disease experience disparities in the diagnosis, treatment, and management of their condition. However, it is unknown whether these sex differences exist with respect to in-hospital patient experience. We examined the comprehensive experience of patients hospitalized due to ischemic heart disease (IHD) across Alberta, Canada, according to sex. METHODS: Patients completed a modified version of the Canadian Patient Experiences Survey-Inpatient Care (CPES-IC) within 6 weeks of discharge. We examined 37 questions, including 33 regarding specific care processes and 4 global rating scales. Survey responses were reported as raw "top-box" percentages, that is, the most-positive answer choice to each question. Odds and corresponding 95% confidence intervals of women reporting a top-box response were then calculated for each question, while controlling for demographic and clinical factors. RESULTS: From April 2014 to March 2020, a total of 5795 surveys (1612 women, 4183 men) were completed. Taking the survey margin of error into account, women had lower top-box percentages on 26 of 37 questions. Similar results were obtained for the adjusted odds of reporting a top-box response. Women did not have a higher percentage of top-box responses on any of the questions studied. CONCLUSIONS: This study is a Canadian first, which stratified the experiences of hospitalized patients living with ischemic heart disease according to sex. Our results highlighted important sex differences. Future research to understand the mechanisms associated with these observed sex differences in patient-reported experiences is warranted.

CONTEXTE: Les femmes atteintes de maladies cardiaques connaissent des disparités en matière de diagnostic, de traitement et de prise en charge de leur maladie. Cependant, on ignore si des différences entre les sexes existent en ce qui concerne l'expérience des patients à l'hôpital. Nous avons examiné l'expérience globale des patients hospitalisés en raison d'une cardiopathie ischémique en Alberta, au Canada, en fonction du sexe. MÉTHODOLOGIE: Les patients ont rempli une version modifiée du Sondage sur les expériences d'hospitalisation des patients canadiens (SEHPC) dans les six semaines suivant leur congé. Nous avons examiné 37 questions, dont 33 concernaient des processus de soins spécifiques, et quatre échelles d'évaluation globale. Les réponses au sondage ont été rapportées sous forme de pourcentages bruts de personnes ayant sélectionné la réponse la plus positive à chaque question. Les rapports de cotes et les intervalles de confiance à 95 % correspondants des femmes ayant sélectionné la réponse la plus positive ont ensuite été calculés pour chaque question, après prise en compte des facteurs démographiques et cliniques. RÉSULTATS: D'avril 2014 à mars 2020, un total de 5 795 sondages (1 612 femmes, 4 183 hommes) ont été remplis. Si l'on tient compte de la marge d'erreur du sondage, la proportion de femmes ayant sélectionné la réponse la plus positive est plus faible pour 26 des 37 questions. Des résultats similaires ont été obtenus pour les rapports de cotes ajustés de la sélection de la réponse la plus positive. Les femmes n'ont eu un pourcentage plus élevé de réponse la plus positive pour aucune des questions étudiées. CONCLUSIONS: Cette étude, pour laquelle on a stratifié par sexe les expériences des patients hospitalisés atteints de cardiopathie ischémique, est une première au Canada. Nos résultats ont mis en évidence d'importantes différences entre les sexes. Des recherches futures sont justifiées pour comprendre les mécanismes associés à ces différences observées entre les sexes dans les expériences signalées par les patients.

The Experience of Parents of Hospitalized Children Living With Medical Complexity.

BACKGROUND AND OBJECTIVES: Children living with medical complexity (CMC) experience frequent hospital admissions. Validated patient-reported experience measures may inform care improvements in this cohort. Our objectives were to examine the comprehensive inpatient experience of CMC by using a validated patient-reported experience measure and compare the results with all other respondents at 2 academic pediatric hospitals in a western Canadian province. METHODS: Parents completed the Child Hospital Consumer Assessment of Healthcare Providers and Systems survey. Surveys were linked with inpatient records, and an accepted case definition was used to extract records pertaining to CMC. Results were reported as percent in "top box," represented by the most positive answer choice to each measure. Odds of reporting a top box response were calculated while controlling for demographic and clinical features. RESULTS: From October 2015 to March 2019, 4197 surveys (1515 CMC; 2682 non-CMC) were collected. Among CMC, the highest-rated measures pertained to being kept informed while in the emergency department, a willingness to recommend the hospital, and parents having a clear understanding of their role in their child's care. The lowest-rated measures pertained to preventing mistakes and reporting concerns and the quietness of the hospital room at night. Compared with others, parents of CMC reported lower raw results on 20 of the 28 measures. They also reported lower a odds of reporting a top box score on 2 measures and higher odds on 1. CONCLUSIONS: Parents of CMC revealed many perceived gaps. These findings can be used to inform strategies to improve care among CMC and policies to support the care of CMC and their families.

Genetic rescue of an insular population of large mammals.

Natural populations worldwide are increasingly fragmented by habitat loss. Isolation at small population size is thought to reduce individual and population fitness via inbreeding depression. However, little is known about the time-scale over which adverse genetic effects may develop in natural populations or the number and types of traits likely to be affected. The benefits of restoring gene flow to isolates are therefore also largely unknown. In contrast, the potential costs of migration (e.g. disease spread) are readily apparent. Management for ecological connectivity has therefore been controversial and sometimes avoided. Using pedigree and life-history data collected during 25 years of study, we evaluated genetic decline and rescue in a population of bighorn sheep founded by 12 individuals in 1922 and isolated at an average size of 42 animals for 10-12 generations. Immigration was restored experimentally, beginning in 1985. We detected marked improvements in reproduction, survival and five fitness-related traits among descendants of the 15 recent migrants. Trait values were increased by 23-257% in maximally outbred individuals. This is the first demonstration, to our knowledge, of increased male and female fitness attributable to outbreeding realized in a fully competitive natural setting. Our findings suggest that genetic principles deserve broader recognition as practical management tools with near-term consequences for large-mammal conservation.

A controlled trial of placebo versus real acupuncture.

UNLABELLED: We sought to determine whether a novel method of placebo acupuncture can be differentiated by subjects from real acupuncture treatment. A single-blind, randomized, controlled clinical trial with an independent observer was performed. Forty-nine healthy subjects over the age of 18 years were randomly assigned to one of 2 experimental groups: 24 subjects received real acupuncture, and 25 subjects received placebo acupuncture. Placebo acupuncture was performed by administering a blunted acupuncture needle through a foam pad at the Large Intestine 4 acupoint. The blunted needle touched but did not penetrate the skin. Real acupuncture was performed by administering an acupuncture needle through a foam pad at the Large Intestine 4 acupoint. The needle pricked and penetrated the skin to a depth of 10 to 20 mm. A simple questionnaire followed, asking whether the subject believed they received real or placebo acupuncture. Twenty-two (88%) of the 25 subjects who received placebo acupuncture believed they received real acupuncture. Nineteen (79.2%) of the 24 subjects who received real acupuncture correctly determined they received real acupuncture. The Fisher exact test showed an insignificant difference between real and placebo acupuncture treatments (P = .463). Subjects were not able to differentiate between real or placebo acupuncture, thereby validating this novel method of administering placebo acupuncture as a good control for acupuncture-naive patients. PERSPECTIVE: The method of placebo acupuncture herein described is a valid control for acupuncture research involving acupuncture-naive patients.

Power of Sign Surveys to Monitor Population Trends.

The urgent need for an effective monitoring scheme for grizzly bear (Ursus arctos) populations led us to investigate the effort required to detect changes in populations of low-density dispersed animals, using sign (mainly scats and tracks) they leave on trails. We surveyed trails in Glacier National Park for bear tracks and scats during five consecutive years. Using these data, we modeled the occurrence of bear sign on trails, then estimated the power of various sampling schemes. Specifically, we explored the power of bear sign surveys to detect a 20% decline in sign occurrence. Realistic sampling schemes appear feasible if the density of sign is high enough, and we provide guidelines for designs with adequate replication to monitor long-term trends of dispersed populations using sign occurrences on trails.

WNT-3a modulates platelet function by regulating small GTPase activity.

Here we provide evidence that WNT-3a modulates platelet function by regulating the activity of four key GTPase proteins: Rap1, Cdc42, Rac1 and RhoA. We observe WNT-3a to differentially regulate small GTPase activity in platelets, promoting the GDP-bound form of Rap1b to inhibit integrin-α(IIb)ß(3) adhesion, while concomitantly increasing Cdc42 and Rac1-GTP levels thereby disrupting normal platelet spreading. We demonstrate that Daam-1 interacts with Dishevelled upon platelet activation, which correlates with increased RhoA-GTP levels. Upon pre-treatment with WNT-3a, this complex disassociates, concurrent with a reduction in RhoA-GTP. Together these data implicate WNT-3a as a novel upstream regulator of small GTPase activity in platelets.

Neonatal renal venous thrombosis: clinical outcomes and prevalence of prothrombotic disorders.

OBJECTIVE: To determine clinical outcomes and the prevalence of prothrombotic conditions in patients who had neonatal renal venous thrombosis (RVT). STUDY DESIGN: A retrospective cohort of neonates with RVT who were admitted to 4 pediatric centers from 1980 to 2001 was identified. Information on clinical presentation, laboratory and radiological investigation, and treatment were abstracted. Survivors were evaluated for renal status and prothrombotic conditions. RESULTS: Forty-three patients with neonatal RVT were identified. RVT was unilateral in 24 patients (56%) and associated with 2thrombi at other sites in 32 patienets (74%). Clinical presentations included renal failure in 24 patients (56%), thrombocytopenia, anemia, or both in 22 patients (51%), and renal mass in 21 patients (49%). Neonatal interventions included anti-coagulants in 28 patients (65%), antihypertensive medications in 9 patients (21%), peritoneal dialysis in 2 patients (5%), and nephrectomy in 2 patients (5%). The median age at follow-up was 3.7 years (range, 0.5-20.2 years). Thirteen patients (34%) had hypertension, and 11 patients (29%) had renal failure. End-stage renal disease developed in 3 patients, and they underwent live-related renal transplants. Twelve of the 28 patients (43%) examined had prothrombotic abnormalities. CONCLUSION: Neonatal RVT is associated with significant renal morbidity and a high prevalence of prothrombotic abnormalities.

Sonographic appearance of bladder malacoplakia.

We report sonographic features of bladder malacoplakia (multiple polypoid solid masses) in a 16-year-old girl with Russell-Silver syndrome who presented with renal failure and urinary tract infection.