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Chlorhexidine skin antisepsis is frequently recommended for most surgical procedures; however, it is unclear if these recommendations should apply to surgery involving traumatic contaminated wounds where povidone-iodine has previously been preferred. We aimed to compare the effect of aqueous 10% povidone-iodine versus aqueous 4% chlorhexidine gluconate on the risk of surgical site infection in patients who required surgery for an open fracture.We conducted a multiple-period, cluster-randomised, crossover trial (Aqueous-PREP) at 14 hospitals in Canada, Spain, and the USA. Eligible patients were adults aged 18 years or older with an open extremity fracture treated with a surgical fixation implant. For inclusion, the open fracture required formal surgical debridement within 72 h of the injury. Participating sites were randomly assigned (1:1) to use either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate immediately before surgical incision; sites then alternated between the study interventions every 2 months. Participants, health-care providers, and study personnel were aware of the treatment assignment due to the colour of the solutions. The outcome adjudicators and data analysts were masked to treatment allocation. The primary outcome was surgical site infection, guided by the 2017 US Centers for Disease Control and Prevention National Healthcare Safety Network reporting criteria, which included superficial incisional infection within 30 days or deep incisional or organ space infection within 90 days of surgery. The primary analyses followed the intention-to-treat principle and included all participants in the groups to which they were randomly assigned. This study is registered with ClinicalTrials.gov, NCT03385304.Between April 8, 2018, and June 8, 2021, 3619 patients were assessed for eligibility and 1683 were enrolled and randomly assigned to povidone-iodine (n=847) or chlorhexidine gluconate (n=836). The trial's adjudication committee determined that 45 participants were ineligible, leaving 1638 participants in the primary analysis, with 828 in the povidone-iodine group and 810 in the chlorhexidine gluconate group (mean age 44·9 years [SD 18·0]; 629 [38%] were female and 1009 [62%] were male). Among 1571 participants in whom the primary outcome was known, a surgical site infection occurred in 59 (7%) of 787 participants in the povidone-iodine group and 58 (7%) of 784 in the chlorhexidine gluconate group (odds ratio 1·11, 95% CI 0·74 to 1·65; p=0·61; risk difference 0·6%, 95% CI -1·4 to 3·4).For patients who require surgical fixation of an open fracture, either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate can be selected for skin antisepsis on the basis of solution availability, patient contraindications, or product cost. These findings might also have implications for antisepsis of other traumatic wounds.US Department of Defense, Canadian Institutes of Health Research, McMaster University Surgical Associates, PSI Foundation.

ImportanceRacial and sex disparities are prevalent in surgical trainees. Although retrospective studies on resident attrition have been conducted for individual specialties, this study analyzes racial and sex differences in resident attrition among all surgical subspecialties over an 18-year period.ObjectiveTo evaluate the racial and sex differences in resident attrition among surgical specialties over an 18-year period.Design, Setting, and ParticipantsThis was a large, cross-sectional, database study that analyzed program-reported resident censuses (program information, resident demographics, and attrition status) obtained by the Association of American Medical Colleges from 2001 to 2018 for trainees in surgical residency programs. Data were analyzed from March 20, 2021, to June 8, 2022.Main Outcomes and MeasuresDemographic trends (including race and ethnicity and sex) for all surgical subspecialty training programs over an 18-year period. Resident attrition includes all-cause withdrawals, dismissals, and transfers to another specialty. Unintended attrition encompasses all withdrawals, dismissals, and transfers except for changing career plans.ResultsThis study included 407 461 program-reported resident years collected from 112 205 individual surgical residents (67 351 male individuals [60.0%]). The mean percentage of female trainees was 40.0% (44 835) and increased over the study period. Sex disparity remained greatest in orthopedic surgery. Residents who were underrepresented in medicine (URiM) comprised 14.9% (16 695) of all surgical trainees but demonstrated a 2.1% decrease over the study period. Overall attrition rate among all specialties was 6.9% (7759), with an unintended attrition rate of 2.3% (2556). Female residents had a significantly higher relative risk (RR) of attrition (RR, 1.16; 95% CI, 1.11-1.22; P P < .001) compared with their male counterparts. URiM residents were at significantly higher RR for attrition (RR, 1.40; 95% CI, 1.32-1.48; P < .001) and unintended attrition (RR, 1.92; 95% CI, 1.75-2.11; P < .001) compared with non-URiM residents. The highest attrition (10.6% [746 of 7043]) and unintended attrition (5.2% [367 of 7043]) rates were in Black/African American residents. The lowest attrition and unintended attrition rates were seen in White residents at 6.2% (4300 of 69 323) and 1.8% (1234 of 69 323), respectively. Black/African American residents were at disproportionate risk for attrition (RR, 1.66; 95% CI, 1.53-1.80; P P P < .001) and unintended attrition (RR, 7.20; 95% CI, 4.84-10.71; P < .001) for Black/African American residents.Conclusions and RelevanceResults of this cross-sectional study suggest that the percentage of female residents in surgical specialties has improved over the last 18 years, and the percentage of URiM residents has remained relatively unchanged. Risk for attrition and unintended attrition was significantly elevated for female and URiM residents, specifically Black/African Americans. These results highlight current racial and sex disparities in resident attrition and demonstrate the importance of developing strategies to recruit, retain, and support residents.

Polyhydroxyalkanoates (PHA), especially poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is considered as the most suitable candidate to replace petrochemical plastics. However, the high production cost and the composition of the monomers in the copolymer are the major constraints in production. The 3-hydroxyvalerate (3HV) rich copolymers are ideal for various applications due to their lower melting points, improved elasticity, and ductility. Haloferax mediterranei is a suitable microorganism for the production of biopolymer PHBV from biowaste. Nevertheless, the potential of H. mediterranei cultivated on food waste as sustainable substrate and levulinic acid as an inducer has not been explored for PHBV production. This study aims at the valorization of food waste as low-cost substrate and evaluation of effect of levulinic acid in the production and composition of PHBV using H. mediterranei. Shake-flask fermentations using different concentrations of salt, glucose and levulinic acid were first performed to optimize the cultivation conditions. The highest growth of the halophile was observed at salt concentration of 15% and glucose of concentration 10 g/L. Under optimized growth conditions, H. mediterranei was cultivated for PHBV production in fed-batch bioreactor with pulse fed levulinic acid. The maximum biomass of 3.19 ± 0.66 g/L was achieved after 140 h of cultivation with 3 g/L of levulinic acid. A decrease in H. mediterranei growth was noticed with the increase in levulinic acid concentration in the range of 3-10 g/L. The overall yield of PHBV at 3, 5, 7 and 10 g/L of levulinic acid were 18.23%, 56.70%, 31.54%, 21.29%, respectively. The optimum concentration of 5 g/L of levulinic acid was found to produce the maximum yield of 56.70% PHBV with 18.55 mol% 3HV content. A correlation between levulinic acid concentrations and PHBV production established in this study can serve as an important reference for future large-scale production.

During the COVID-19 pandemic, WHO and CDC suggest people stay 1 m and 1.8 m away from others, respectively. Keeping social distance can avoid close contact and mitigate infection spread. Many researchers suspect that suggested distances are not enough because aerosols can spread up to 7-8 m away. Despite the debate on social distance, these social distances rely on unobstructed respiratory activities such as coughing and sneezing. Differently, in this work, we focused on the most common but less studied aerosol spread from an obstructed cough. The flow dynamics of a cough jet blocked by the backrest and gasper jet in a cabin environment was characterized by the particle image velocimetry (PIV) technique. It was proved that the backrest and the gasper jet can prevent the front passenger from droplet spray in public transportation where maintaining social distance was difficult. A model was developed to describe the cough jet trajectory due to the gasper jet, which matched well with PIV results. It was found that buoyancy and inside droplets almost do not affect the short-range cough jet trajectory. Infection control measures were suggested for public transportation, including using backrest/gasper jet, installing localized exhaust, and surface cleaning of the backrest.

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use(1). Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels(2), heart disease remains the leading cause of death worldwide(3). Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS(4-23) have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns(24). Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine(25), we anticipate that increased diversity of participants will lead to more accurate and equitable(26) application of polygenic scores in clinical practice.

Objectives To describe the characteristics of parent knowledge needs and skill acquisition over the course of their infant’s neonatal intensive care unit hospitalization. Methods 148 parents/guardians of infants ≤33 week gestation enrolled during the usual care phase of a multi-site quasi-experimental study, completing weekly surveys about their learning needs for the coming week and skills learned in the past week. Results The topics of most interest or concern for parents included feeding their infant and their infant’s medical course. Knowledge needs varied by phase of hospitalization (early, middle, late) and by parent age, prior parenting experience, infant gestational age and hospital length of stay. The most common skills learned related to feeding and basic infant care. The number of skills parents reported learning each week varied by parent age, gender, and education. Conclusions Parents of preterm infants expressed specific learning needs and acquisition of skills that varied over the course of the hospitalization and by parent and infant characteristics. Practice implications The findings can be used to improve parent learning experiences so that they can become full partners in their infant’s caregiving and are better prepared to care for their infant after discharge. Study registration ClinicalTrials.gov , ID NCT03418870.

Background. Human papillomavirus (HPV) vaccination was introduced into the routine immunization schedule in the United States in late 2006 for females aged 11 or 12 years with catch-up vaccination recommended for those aged 13-26 years. In 2010 3-dose vaccine coverage was only 32% among 13-17 year-olds. Reduction in the prevalence of HPV types targeted by the quadrivalent vaccine (HPV-6 -11 -16 and -18) will be one of the first measures of vaccine impact. Methods. We analyzed HPV prevalence data from the vaccine era (2007-2010) and the prevaccine era (2003-2006) that were collected during National Health and Nutrition Examination Surveys. HPV prevalence was determined by the Linear Array HPV Assay in cervicovaginal swab samples from females aged 14-59 years; 4150 provided samples in 2003-2006 and 4253 provided samples in 2007-2010. Results. Among females aged 14-19 years the vaccine-type HPV prevalence (HPV-6 -11 -16 or -18) decreased from 11.5% (95% confidence interval [CI] 9.2-14.4) in 2003-2006 to 5.1% (95% CI 3.8-6.6) in 2007-2010 a decline of 56% (95% CI 38-69). Among other age groups the prevalence did not differ significantly between the 2 time periods (P > .05). The vaccine effectiveness of at least 1 dose was 82% (95% CI 53-93). Conclusions. Within 4 years of vaccine introduction the vaccine-type HPV prevalence decreased among females aged 14-19 years despite low vaccine uptake. The estimated vaccine effectiveness was high.

As immunization programs for human papillomavirus (HPV) are implemented more widely around the world, interest is increasing in measuring their impact. One early measurable impact of HPV vaccine is on the prevalence of specific HPV types in a population. In low-resource settings, a potentially attractive strategy would be to monitor HPV prevalence using clinical cervical cancer screening test results to triage specimens for HPV typing. We assessed this approach in a nationally representative population of U.S. females aged 14–59 years. Using self-collected cervico-vaginal swab specimens from 4,150 women participating in the National Health and Nutrition Examination Survey during 2003–2006, we evaluated type-specific HPV prevalence detected by the Roche linear array (LA) research test on all specimens, compared with type-specific HPV prevalence detected by LA conducted only on specimens positive by the digene hybrid capture 2 (HC-2) clinical test. We calculated weighted prevalence estimates and their 95% confidence intervals (CIs), and examined relative type-specific HPV prevalence according to the two testing approaches. The population prevalence of oncogenic HPV vaccine types 16/18 was 6.2% (CI:5.4–7.1) by LA if all specimens were tested, and 2.4% (CI:1.9–3.0) if restricted to positive HC-2. Relative prevalence of individual HPV types was similar for both approaches. Compared with typing all specimens, a triage approach would require testing fewer specimens, but a greater reduction in HPV prevalence or a larger group of specimens would be needed to detect vaccine impact. Further investigation is warranted to inform type-specific HPV monitoring approaches around the world.

Background: Obesity has been described among survivors of pediatric Acute Lymphoblastic Leukemia (ALL), especially those who have received cranial radiation. This study aims to evaluate the prevalence of overweight or obesity in pediatric ALL survivors who were not exposed to radiation, identify the time frame in which the rate of obesity rise is the greatest, and identify contributing clinical and treatment variables. Methods: In this retrospective, single institution study, the charts of 132 ALL survivors were reviewed. Odds Ratios (OR) and 95% Confidence Intervals (CI) were calculated for being overweight or obese at their 2 year follow-up for the following clinical variables: ethnicity, age at diagnosis, and weight at diagnosis. Changes in BMI percentiles between 4 different time points were assessed using t-test comparison and p values. Results: Survivors of ALL were more likely to be overweight or obese than the general population at the 2 and 5 year follow-up. White and Hispanic ethnicity and being overweight or obese at diagnosis were also risk factors for being overweight or obese 2 years after the end of treatment. When looking at the time frame of weight gain, survivors had a significant increase in BMI percentile between diagnosis and end of therapy, and between diagnosis and 2 year follow-up, but did not have a significant increase between end of therapy and 2 year follow-up. Conclusion: Patients with ALL have an increased risk of being obese at follow-up. They show early weight gain, between diagnosis and end of treatment, and remain overweight/obese long term. Ethnicity and BMI weight category at diagnosis were significant influences. A strategic plan to prevent this weight gain should be implemented early during therapy.

Understanding of preadolescent sexuality is limited. To help fill this gap, we calculated frequencies, percentages, and confidence intervals for 1,096 preadolescents’ reports of sexual thoughts, intentions, and sexual behavior. Cochran-Armitage trend tests accounted for age effects. Findings show that 9-year-olds are readying for sexual activity, with sexual readiness increasing between ages of 9 and 12. Sexual thoughts increased with age ( p < .001): 46% of 9-year-olds and 70% of 12-year-olds were ready to learn about sex, and 14% of 9-year-olds and 41% of 12-year-olds thought about having sex. Few 9-year-olds anticipated sexual debut, but this increased with age ( p < .05): 25% of 12-year-olds were ready for sex, and 20% anticipated initiating sex within a year. Our results indicate that preadolescents are initiating dating relationships and anticipating intercourse, and some have engaged in risk behaviors. Thus preadolescence is a critical time to implement prevention programs.

Background Asparaginase is a key component of pediatric therapy for Acute lymphoblastic leukemia (ALL). Two formulations available in the USA are pegylated E. coli asparaginase (PEG) and Erwinia chrysanthemi asparaginase (Erwinaze). Hypersensitivity reactions have been observed in ~ 20% of patients receiving PEG. Patients with overt symptoms of hypersensitivity are typically switched to Erwinaze. In cases of hypersensitivity, anti-asparaginase antibodies may be present that neutralize circulating asparaginase and in some cases may present without clinical signs, a phenomenon known as silent inactivation. Few studies have prospectively evaluated the incidence of silent inactivation in pediatric ALL patients. In this prospective study, we performed therapeutic drug monitoring of asparaginase levels on newly diagnosed pediatric ALL patients to determine the incidence of silent inactivation and to switch patients to Erwinaze, if silent inactivation was detected. Methods A prospective study was conducted at CHOC Children's Hospital on patients with newly diagnosed ALL or lymphoblastic lymphoma between 2016 to 2018. Patients designated as high or very high risk B-ALL post induction, T-ALL and B/T lymphoblastic lymphoma were enrolled. Patients received therapy on or according to a COG protocol with PEG (2500 IU/m2) administered via 2-hour i.v. infusion without antihistamine or steroid premedication. Asparaginase activity was measured days 7 and 14 after each of the two PEG doses during Consolidation. Serum asparaginase level of >0.1 IU/ml and >0.02 IU/ml was considered therapeutic at 7 or 14 days post PEG, respectively. Silent inactivation was defined as serum asparaginase levels below these values without signs of overt allergy. Any patient found to have silent inactivation was immediately switched to Erwinaze. Patient characteristics, common adverse events associated with asparaginase and serum asparaginase levels were analyzed. Descriptive statistics and Pearson's coefficient was used for analysis. Results Thirty-nine patients were enrolled with a mean age of 9.8 years (range, 1-23) with the majority being B-ALL (87.2%) of which 3 were Ph-like (Table 1). Twelve patients (30.7%) had overt hypersensitivity and one patient (2.6%) had silent inactivation. One patient had overt hypersensitivity after completion of the PEG infusion with a measured asparaginase level 7 days post that was therapeutic. One-hundred fifteen drug levels were collected, for an average of 2.9 levels per patient (maximum 4 levels). There was a difference in mean asparaginase activity in patients without hypersensitivity compared to those with hypersensitivity (1.110 IU/mL versus 0.737 IU/mL, respectively, p=.0095). There were no significant differences in asparaginase levels based on age, gender or BSA. The highest asparaginase level observed was 7 days post the 2nd dose of asparaginase in Consolidation. Overall, the incidence of patients with CTCAE grade ≥2 transaminitis was 51.3% (n=20), hyperglycemia 2.6 % (n=1), hyperbilirubinemia 5.1% (n=2), and thrombosis 2.6% (n=1). Pancreatitis of any grade was not observed in this cohort. Discussion We detected silent inactivation in a single patient who had an asparaginase level of 0.01 seven days after the first dose of PEG and showed no signs of overt allergic reaction. This patient was switched to Erwinaze and an asparaginase level drawn 48 hours post Erwinaze was therapeutic at 0.719. Another patient developed a hypersensitivity reaction 12-hours after PEG and had a serum asparaginase level of 1.29 7-days post PEG. This suggests that not all anti-asparaginase antibodies are neutralizing since this patient continued to demonstrate therapeutic drug levels. The incidence of allergic reactions to PEG at our institution appears higher than reported in prior studies. Our data shows a statistically significant difference between serum asparaginase levels in patients with and without hypersensitivity. Our study also shows that silent inactivation exists in a very small proportion of patients. Additionally, patients who develop late allergic reactions to PEG may still have therapeutic asparaginase levels. Thus, monitoring of asparaginase levels may be warranted to detect silent inactivation and to monitor asparaginase levels in patients who develop delayed hypersensitivity. A larger prospective study is needed to confirm these results. Disclosures No relevant conflicts of interest to declare.

Objective: The Wnt/β-catenin pathway is a major signal transduction pathway involved in ovarian cancer (OVCA) metastasis and resistance to chemotherapy. This pathway downregulates protective immunity mediated by intra-tumoral CD8+T cells in other cancer types. WNT974 is a novel drug that inhibits the enzyme Porcupine, which controls Wnt protein secretion. Our objective was to measure the effect of WNT974 alone and in combination with dose dense paclitaxel (ddPac) on tumor growth and on infiltrating CD8+ T cells in two syngeneic OVCA mouse models. Methods: C57BL/6 mice were injected subcutaneously (SC) (n=20) or intraperitoneally (IP) (n=24) with 7 x 106 ID8 mouse OVCA cells. Mice were treated with vehicle control, ddPac, WNT974, or the combination (combo). C57BL/6 TgMISIIR-Tag-Low transgenic mice were injected with 7 x 106 MOVCAR cells IP (n=8) and treated with vehicle control or combo. WNT974 was given by oral gavage twice a day (5mg/kg for 7 days then decreased to 2.5mg/kg twice a day for up to 4 weeks). Paclitaxel was given IP (5mg/kg) 3 days on and 3 days off for a total of 9 doses. SC tumors were measured with calipers twice per week. In the IP model, mice were sacrificed after 13 days of treatment and tumor weights and ascites volume were determined. Flow cytometry was used to evaluate the presence of CD8+ T cells in IP tumors. Results: In the ID8 SC model, combo therapy reduced tumor size compared to vehicle control (18 vs. 40mm2, p Conclusions: The combination of WNT974 and ddPac reduced tumor size and increased tumor infiltration of CD8+ T cells in syngeneic OVCA mouse models. This suggests that the improved response observed with the ddPac and WNT974 combination is in part due to upregulation of the intra-tumoral immune response. Further investigation of this pathway is warranted as an immune modulator and a potential therapeutic target in ovarian cancer. Citation Format: David W. Doo, Angelina I. Londono, Dylana J. Moore, Selene Meza-Perez, Ashwini A. Katre, Tyler R. McCaw, Haller J. Smith, Carol Y. Lin, Sara J. Cooper, J Michael Straughn, Donald J. Buchsbaum, Lyse A. Norian, Troy D. Randall, Rebecca C. Arend. The effect of Wnt inhibition combined with paclitaxel on tumor burden and CD8+ T cell infiltration in syngeneic murine models of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4710.

A randomly selected nationally representative sample of 508 practicing pediatricians was surveyed in order to identify factors associated with physician delivery of primary prevention to parents about sexual risk reduction (SRR). A full 86% (n = 435) reported that provision of SRR guidance is equally or more important than other guidance provided to parents. Among the 435, only 121 (28%) provided SRR guidance to >75% of parents of their adolescent patients. Multivariate analyses revealed barriers of: lack of training, lack of request from parents, and awkwardness. To promote parent–child communication, physicians suggested high-quality brochures for parents (84%); a list of resources (74%); and tools to facilitate parent–child discussions (63%). Pediatricians and parents are important components of sexual risk prevention efforts for adolescents. Editors’ Strategic Implications: The findings related to the perceived importance—but infrequent delivery—of SRR communication between pediatricians and parents of adolescents have implications for training and information dissemination in pediatric practices, as well as other health and reproductive health settings.

During endochondral bone development, both the chondrogenic differentiation of mesenchyme and the hypertrophic differentiation of chondrocytes coincide with the proliferative arrest of the differentiating cells. However, the mechanisms by which differentiation is coordinated with cell cycle withdrawal, and the importance of this coordination for skeletal development, have not been defined. Through analysis of mice lacking the pRB-related p107 and p130 proteins, we found that p107 was required in prechondrogenic condensations for cell cycle withdrawal and for quantitatively normal α1(II) collagen expression. Remarkably, the p107-dependent proliferative arrest of mesenchymal cells was not needed for qualitative changes that are associated with chondrogenic differentiation, including production of Alcian blue-staining matrix and expression of the collagen IIB isoform. In chondrocytes, both p107 and p130 contributed to cell cycle exit, and p107 and p130 loss was accompanied by deregulated proliferation, reduced expression of Cbfa1, and reduced expression of Cbfa1-dependent genes that are associated with hypertrophic differentiation. Moreover, Cbfa1 was detected, and hypertrophic differentiation occurred, only in chondrocytes that had undergone or were undergoing a proliferative arrest. The results suggest that Cbfa1 links a p107- and p130-mediated cell cycle arrest to chondrocyte terminal differentiation.

Osteosarcoma (OS) is the most common primary bone malignancy diagnosed in children and adolescents with a high propensity for local invasion and distant metastasis. Despite current multidisciplinary treatments, there has not been a drastic change in overall prognosis within the last two decades. With current treatments, 60-70 % of patients with localized disease survive. Given a propensity of Wnt signaling to control multiple cellular processes, including proliferation, cell fate determination, and differentiation, it is a critical pathway in OS disease progression. At the same time, this pathway is extremely complex with vast arrays of cross-talk. Even though decades of research have linked the role of Wnt to tumorigenesis, there are still outstanding areas that remain poorly understood and even controversial. The canonical Wnt pathway functions to regulate the levels of the transcriptional co-activator β-catenin, which ultimately controls key developmental gene expressions. Given the central role of this mediator, inhibition of Wnt/β-catenin signaling has been investigated as a potential strategy for cancer control. In OS, several secreted protein families modulate the Wnt/β-catenin signaling, including secreted Frizzled-related proteins (sFRPs), Wnt inhibitory protein (WIF), Dickkopf proteins (DKK-1,2,3), sclerostin, and small molecules. This chapter focuses on our current understanding of Wnt/β-catenin signaling in OS, based on recent in vitro and in vivo data. Wnt activates noncanonical signaling pathways as well that are independent of β-catenin which will be discussed. In addition, stem cells and their association with Wnt/β-catenin are important factors to consider. Ultimately, the multiple canonical and noncanonical Wnt/β-catenin agonists and antagonists need to be further explored for potential targeted therapies.

Communication Technology and Social Change is a distinctive collection that provides current theoretical, empirical, and legal analyses for a broader understanding of the dynamic influences of communication technology on social change. With a distinguished panel of contributors, the volume presents a systematic discussion of the role communication technology plays in shaping social, political, and economic influences in society within specific domains and settings.

Wnt molecules are a class of cysteine-rich secreted glycoproteins that participate in various developmental events during embryogenesis and adult tissue homeostasis. Since its discovery in 1982, the roles of Wnt signaling have been established in various key regulatory systems in biology. Wnt signals exert pleiotropic effects, including mitogenic stimulation, cell fate specification, and differentiation. The Wnt signaling pathway in humans has been shown to be involved in a wide variety of disorders including colon cancer, sarcoma, coronary artery disease, tetra-amelia, Mullerian duct regression, eye vascular defects, and abnormal bone mass. The canonical Wnt pathway functions by regulating the function of the transcriptional coactivator β-catenin, whereas noncanonical pathways function independent of β-catenin. Although the role of Wnt signaling is well established in epithelial malignancies, its role in mesenchymal tumors is more controversial. Some studies have suggested that Wnt signaling plays a pro-oncogenic role in various sarcomas by driving cell proliferation and motility; however, others have reported that Wnt signaling acts as a tumor suppressor by committing tumor cells to differentiate into a mature lineage. Wnt signaling pathway also plays an important role in regulating cancer stem cell function. In this review, we will discuss Wnt signaling pathway and its role in osteosarcoma.

The relationship between cause and timing of death in 294 adults who had been hospitalized with community-acquired bacterial meningitis was investigated. For 74 patients with community-acquired bacterial meningitis who died during hospitalization, the underlying and immediate causes of death were identified according to the criteria of the World Health Organization and National Center for Health Statistics. Patients were classified into 3 groups: category I, in which meningitis was the underlying and immediate cause of death (59% of patients; median duration of survival, 5 days); category II, in which meningitis was the underlying but not immediate cause of death (18%; median duration of survival, 10 days); and category III, in which meningitis was neither the underlying nor immediate cause of death (23%; median duration of survival, 32 days). In a substantial proportion of adults hospitalized with community-acquired bacterial meningitis, meningitis was neither the immediate nor the underlying cause of death. A 14-day survival end point discriminated between deaths attributable to meningitis and those with another cause.

Osteosarcoma (OS) is the most common primary bone malignancy with a high propensity for local invasion and distant metastasis. Despite current multidisciplinary treatments, there has not been a drastic change in overall prognosis within the past 2 decades. Dickkopf-3 protein (Dkk-3/REIC) has been known to inhibit canonical Wnt/β-catenin pathway, and its expression has been shown to be downregulated in OS cell lines. Usingin vivoandin vitrostudies, we demonstrated that Dkk-3-transfected 143B cells inhibited tumorigenesis and metastasis in an orthotopic xenograft model of OS. Inoculation of Dkk-3-transfected 143B cell lines into nude mice showed significant decreased tumor growth and less metastatic pulmonary nodules (88.7%) compared to the control vector.In vitroexperiments examining cellular motility and viability demonstrated less anchorage-independent growth and decreased cellular motility for Dkk-3-transfected 143B and SaOS2 cell lines compared to the control vector. Downstream expressions of Met, MAPK, ALK, and S1004A were also downregulated in Dkk-3-transfected SaOS2 cells, suggesting the ability of Dkk-3 to inhibit tumorigenic potential of OS. Together, these data suggest that Dkk-3 has a negative impact on the progression of osteosarcoma. Reexpressing Dkk-3 in Dkk-3-deficient OS tumors may prove to be of benefit as a preventive or therapeutic strategy.

C-reactive protein (CRP) is a prototypic acute phase reactant in humans and rabbits whose serum concentration can increase up to 1000-fold following an acute inflammatory stimulus. CRP binds to many phosphate ester-containing compounds including phosphorylcholine, nucleotides, chromatin and snRNP. To examine the in vivo function of this protein, we produced transgenic mice capable of significant CRP synthesis. In contrast to most other vertebrates, mice synthesize CRP in only trace amounts. The transgenic animals express rabbit CRP from either the phosphoenolpyruvate carboxykinase promoter (PEPCK-CRP) or the mouse metallothionein I promoter (MT-CRP). Manipulating the diet in one of the PEPCK-CRP lines led to a rise in serum CRP levels from < 5 mu g/mL to 100-200 mu g/mL over a period of 2 days. The two MT-CRP lines examined expressed CRP constitutively which could be further elevated 2-4-fold following an inflammatory stimulus. Transgenic CRP bound phosphorylcholine was pentameric, had a circulating half-life of 30-60 min and was capable of activating mouse complement when bound to a ligand. We conclude that these transgenic lines express CRP with many of the properties of authentic rabbit CRP, and that the expression of CRP can be controlled to be dependent or independent of the acute phase response.

Options for treating disseminated Mycobacterium avium complex (MAC) disease have improved. However, efficacy is not always certain, resistance is common and rapidly bactericidal agents would improve efficacy and prevent resistance. Certain oxazolidinones were tested against MAC strains and inhibited growth at expected serum concentrations or lower. Activity correlated with hydrophobicity and one agent was bactericidal at concentrations two to five times greater than the MIC.

Objective To provide HIV seroincidence data among men who have sex with men (MSM) in the United States and to identify predictive factors for seroconversion. Methods From 1998–2002, 4684 high-risk MSM, age 18–60 years, participated in a randomized, placebo-controlled HIV vaccine efficacy trial at 56 U.S. clinical trial sites. Demographics, behavioral data, and HIV status were assessed at baseline and 6 month intervals. Since no overall vaccine efficacy was detected, data were combined from both trial arms to calculate HIV incidence based on person-years (py) of follow-up. Predictors of seroconversion, adjusted hazards ratio (aHR), were evaluated using a Cox proportional hazard model with time-varying covariates. Results Overall, HIV incidence was 2.7/100 py and was relatively uniform across study sites and study years. HIV incidence was highest among young men and men reporting unprotected sex, recreational drug use, and a history of a sexually transmitted infection. Independent predictors of HIV seroconversion included: age 18–30 years (aHR = 2.4; 95% CI 1.4,4.0), having >10 partners (aHR = 2.4; 95% CI 1.7,3.3), having a known HIV-positive male sex partner (aHR = 1.6; 95% CI 1.2, 2.0), unprotected anal intercourse with HIV positive/unknown male partners (aHR = 1.7; 95% CI 1.3, 2.3), and amphetamine (aHR = 1.6; 95% CI 1.1, 2.1) and popper (aHR = 1.7; 95% CI 1.3, 2.2) use. Conclusions HIV seroincidence was high among MSM despite repeated HIV counseling and reported declines in sexual risk behaviors. Continuing development of new HIV prevention strategies and intensification of existing efforts will be necessary to reduce the rate of new HIV infections, especially among young men.

We examine efficacy of the Parents Matter! Program (PMP), a program to teach African-American parents of preadolescents sexual communication and HIV-prevention skills, through a multicenter, randomized control trial. A total of 1115 parent-child participants were randomized to one of three intervention arms (enhanced, brief, control). Percentages and 95% confidence intervals compare parents' perception of child readiness to learn about sexual issues, communication effectiveness, and dyad concordance from baseline to 12 months postintervention. Wilcoxon rank sum tests compare the changes in scores measuring communication content in HIV/AIDS, abstinence, and condom use. Compared to control, parents in the enhanced arm increased perception of child readiness to learn about sex (16% vs. 29%; p < .001), and a greater proportion of parent-child dyads reported concordant responses on communication topics: HIV/AIDS (15%, 95% CI = 8-21%; p < .001), abstinence (13%, 95% CI = 7-20%; p < .001), condoms (15%, 95% CI = 9-22%; p < .001). Increases in communication scores in HIV/AIDS, abstinence, and condom use were greater in the enhanced arm than control (p < 0.01). We conclude that the enhanced PMP can help parents educate children about HIV and prepare children to avoid sexual risk.

This study explored parent–child communication about HIV/AIDS among two populations disproportionately affected by HIV. Similar computer-assisted surveys were completed by parents of pre-teens, including 1,115 African American parents of 9–12-year-old children in southeastern US and 403 parents of 10–12-year-old children in Nyanza Province, Kenya. Multivariate analyses identified factors associated with parental report of ever talking to their child about HIV/AIDS. Twenty-nine percent of US parents and 40% in Kenya had never talked to their pre-teen about HIV/AIDS. In both countries, communication was more likely if parents perceived their child to be ready to learn about sex topics, had gotten information to educate their child about sex, and had greater sexual communication responsiveness (skill, comfort, and confidence communicating about sexuality). Programs are needed that help parents assess children’s readiness to learn about sexual issues; access accurate information about adolescent sexual risks; and acquire the responsiveness needed to discuss sexual issues, including HIV/AIDS.

Continuous spinal opiate administration via permanently implantable drug delivery devices has been proven to provide profound analgesia for chronic pain conditions. We present a case in which the catheter of an implantable subarachnoid device was misplaced into the subdural/extra-arachnoid space despite the free flow of cerebrospinal fluid. This was verified by x-ray dye studies. It is postulated that this misplacement of the catheter likely occurred as a result of recent lumbar punctures the patient had undergone. Extravasation of cerebrospinal fluid created a false space and contributed to the misplacement and ultimate failure of the device to provide analgesia.

The long terminal repeat (LTR) of Moloney murine sarcoma virus (Mo-MuSV) was used as a model system to study the stress response of mammalian cells to physical carcinogens. The chloramphenicol acetyltransferase (CAT) gene was inserted between two Mo-MuSV LTRs, and the LTR-CAT-LTR construct was used for virus production and was integrated into the genome of NIH 3T3 cells in the proviral form. This construct was used to assure that the integrated CAT gene was driven by the promoter of the LTR. Expression of the CAT gene was stimulated 4-fold by UV irradiation, and the peak of activity was observed at 18 hr. In contrast, stimulation of the CAT expression after x-irradiation was 2-fold and occurred at 6 hr. Phorbol myristate acetate also stimulated CAT activity 4-fold with a peak at 6 hr. Down-regulation of protein kinase C blocked totally the response to x-irradiation but only partially the response to UV. The protein kinase inhibitor H7 blocked the response to treatment by UV, x-ray, and phorbol ester.

Background Human papillomavirus (HPV) vaccination was introduced into the adolescent immunisation schedule in the United States in mid 2006. Vaccination is recommended for females at age 11 or 12 years and through age 26 if not previously vaccinated. Estimated 3-dose coverage was 32% among 13–17 year-olds in 2010. Objectives To compare HPV prevalence among females in the first 4 years of the vaccine era (2007–2010) with the prevaccine era (2003–2006), and to determine vaccine effectiveness (VE). Methods The National Health and Nutrition Examination Surveys (NHANES) are a series of cross sectional surveys, designed to be nationally representative of the civilian, non-institutionalised US population. HPV prevalence was determined in self-collected cervicovaginal swabs from females aged 14–59 years; 4150 in 2003–2006 and 4253 in 2007–2010. Type-specific HPV prevalence was determined by the Linear Array HPV Genotyping Assay. VE was estimated among sexually active 14–26 year-olds in 2007–2010. Results Among females aged 14–19 years, vaccine type (VT) HPV prevalence decreased from 11.5% (95% CI = 9.2, 14.4) in 2003–2006 to 5.1% (95% CI = 3.8, 6.6) in 2007–2010; a 56% (95% CI = 37%, 69%) decline. Prevalence did not differ between the two time periods in other age groups. History of vaccination was associated with lower VT HPV prevalence among sexually active 14–19 years-olds, 3.5% vs. 12.6% (aRR = 0.18; 95% CI, 0.7–0.48, estimated VE = 82%) and among 20–26 year-olds, 12.4% vs 21.3% (aRR = 0.46; 95% CI, 0.22–0.99, estimated VE = 54%). Our sample size was too small to evaluate effectiveness by number of doses. Conclusions Within 4 years of vaccine introduction, there was a decrease in VT HPV prevalence in a nationally representative sample of females aged 14–19 years. As expected, VE was lower among those vaccinated at older ages. Ongoing monitoring will allow assessment of vaccine impact on prevalence, possible cross protection or type replacement.

Objective To evaluate the efficacy of a parent-based sexual-risk prevention program for African American preadolescents. Design Randomized controlled trial. Setting Community-based study conducted in Athens, Georgia; Atlanta, Georgia; and Little Rock, Arkansas from 2001 to 2004. Participants From 1545 inquiries, 1115 African American parent-preadolescent dyads (child, aged 9-12 years) formed the analytic sample. Intervention Participants were randomized into 1 of 3 study arms: enhanced communication intervention (five 2½-hour sessions), single-session communication intervention (one 2½-hour session), and general health intervention (control, one 2½-hour session). Outcome Measures Continuous measures of parent-preadolescent sexual communication and parental responsiveness to sex-related questions at preintervention, postintervention, and at 6- and 12-month follow-ups; and dichotomous measure of preadolescent sexual risk (having engaged in or intending to engage in sexual intercourse at 12-month follow-up). Results Using intent-to-treat participants, differences of mean change from baseline for continuous measures and relative risk for the dichotomous measure of sexual risk were calculated. Participants in the enhanced intervention had higher mean changes from baseline scores, indicating more sexual communication and responsiveness to sexual communication at each assessment after intervention for all continuous measures than those in the control intervention and single-session intervention. Preadolescents whose parents attended all 5 sessions of the enhanced intervention had a likelihood of sexual risk at the 12-month follow-up of less than 1.00 relative to those whose parents attended the control (relative risk, 0.65; 95% confidence interval, 0.41-1.03) and single-session (relative risk, 0.62; 95% confidence interval, 0.40-0.97) interventions. Conclusions These results provide preliminary evidence for the efficacy of a parenting program designed to teach sexual communication skills to prevent sexual risk in preadolescents. Trial Registration clinicaltrials.govIdentifier: NCT00137943