The relationship of school climate, teacher defending and friends on students' perceptions of bullying in high school.

The purpose of this study was to examine the relationship of school climate, teacher defending, and friends on bullying and victimization. Participants were 2273 high school students from 3 public schools (an all girls, all boys boarding, and a co-ed day) in Kenya. A structural equation model was used to examine relationships between school climate, teacher behavior toward bullying, and student demographic characteristics, and bullying. Results revealed that a positive school climate was associated with less bullying behavior and victimization. In addition, when students reported that teachers stop bullying by students, bullying behavior and victimization scores were lower. Contrary to previous research these results showed that residents of a boys only boarding school were less likely to report bullying behavior than residents of an all girls school, or students at a co-educational institution. Furthermore, there were no differences in bullying behavior or victimization by gender or grade level. Implications of these results are discussed.

Profiling the relationship between tumor-associated macrophages and pharmacokinetics of liposomal agents in preclinical murine models.

The mononuclear phagocyte system (MPS) has previously been shown to significantly affect the clearance, tumor delivery, and efficacy of nanoparticles (NPs). This study profiled MPS cell infiltration in murine preclinical tumor models and evaluated how these differences may affect tumor disposition of PEGylated liposomal doxorubicin (PLD) in models sensitive and resistant to PLD. Significant differences in MPS presence existed between tumor types (e.g. ovarian versus endometrial), cell lines within the same tumor type, and location of tumor implantation (i.e. flank versus orthotopic xenografts). Further, the differences in MPS presence of SKOV-3 ovarian and HEC1A endometrial orthotopic cancer models may account for the 2.6-fold greater PLD tumor exposure in SKOV-3, despite similar plasma, liver and spleen exposures. These findings suggest that profiling the presence of MPS cells within and between tumor types is important in tumor model selection and in tumor types and patients likely to respond to NP treatment.

Roles of chemokines CCL2 and CCL5 in the pharmacokinetics of PEGylated liposomal doxorubicin in vivo and in patients with recurrent epithelial ovarian cancer.

Nanoparticles (NPs) are cleared by monocytes and macrophages. Chemokines CCL2 and CCL5 are key mediators for recruitment of these immune cells into tumors and tissues. The purpose of this study was to investigate effects of CCL2 and CCL5 on the pharmacokinetics (PKs) of NPs. Mice deficient in CCL2 or CCL5 demonstrated altered clearance and tissue distribution of polyethylene glycol tagged liposomal doxorubicin (PLD) compared to control mice. The PK studies using mice bearing SKOV3 ovarian cancer xenografts revealed that the presence of tumor cells and higher expression of chemokines were significantly associated with greater clearance of PLD compared to non-tumor bearing mice. Plasma exposure of encapsulated liposomal doxorubicin positively correlated with the total exposure of plasma CCL2 and CCL5 in patients with recurrent epithelial ovarian cancer treated with PLD. These data emphasize that the interplay between PLD and chemokines may have an important role in optimizing PLD therapy. FROM THE CLINICAL EDITOR: The use of nanoparticles as drug delivery carriers is gaining widespread acceptance in the clinical setting. However, the underlying pharmacokinetics of these novel drugs has not really been elucidated. In this interesting article, the authors carried out experiments using mice deficient in CCL2 or CCL5 to study the clearance of liposomal system. They showed the important role the immune system played and would enable better designs of future drug delivery systems.

Meta-analysis of inter-patient pharmacokinetic variability of liposomal and non-liposomal anticancer agents.

A meta-analysis was conducted to evaluate the inter-patient pharmacokinetic (PK) variability of liposomal and small molecule (SM) anticancer agents. Inter-patient PK variability of 9 liposomal and SM formulations of the same drug was evaluated. PK variability was measured as coefficient of variance (CV%) of area under the plasma concentration versus time curve (AUC) and the fold-difference between AUCmax and AUCmin (AUC range). CV% of AUC and AUC ranges were 2.7-fold (P<0.001) and 16.7-fold (P=0.13) greater, respectively, for liposomal compared with SM drugs. There was an inverse linear relationship between the clearance (CL) of liposomal agents and PK variability with a lower CL associated with greater PK variability (R(2)=0.39). PK variability of liposomal agents was greater when evaluated from 0-336 h compared with 0-24h. PK variability of liposomes is significantly greater than SM. The factors associated with the PK variability of liposomal agents need to be evaluated. FROM THE CLINICAL EDITOR: In this meta-analysis, the inter-patient pharmacokinetic variability of 9 liposomal and small molecule anti-cancer agents was studied. The authors determined that several parameters are in favor of the liposomal formulation; however, the PK variability of the formulation was higher compared with small molecule agents, the reason for which remains to be determined in future studies.

Comparison of Adolescent Meningococcal B Vaccination Rates in Four Diverse Outpatient Clinics.

OBJECTIVE: Meningococcal disease, caused by Neisseria meningitidis, is associated with severe illness and death. The Centers for Disease Control and Prevention Advisory Committee on Immunization Practices have published recommendations for the use of meningococcal vaccines in the United States. The primary objective of this study is to compare meningococcal serogroup B vaccination rates among adolescents at 4 diverse outpatient clinics. METHODS: In this retrospective chart review, patients between the ages of 16 and 23 years were identified by using automated dispensing cabinet records of meningococcal serogroup ACWY vaccine removal. Immunization records were reviewed to determine if meningococcal serogroup B vaccine had been administered. Patients from 2 pediatric clinics and 2 family medicine clinics were included in our analysis. RESULTS: Two hundred sixty-five patients were identified for review and 134 patients were included in our study. Of these, 43 (32%) had received the full meningococcal serogroup B vaccine series and 32 (24%) had completed the vaccine series for both meningococcal serogroup B and meningococcal serogroup ACWY series. Most patients who had completed a meningococcal serogroup B vaccine series presented to a pediatric clinic. CONCLUSIONS: Less than half of adolescent patients completed their meningococcal B vaccine series at 4 diverse outpatient clinics, with a greater number of patients receiving vaccinations at pediatric clinics than family medicine clinics. Our findings highlight a need for increased education to providers regarding the current meningococcal B vaccination recommendations.

Distracted pedestrian behavior: An observational study of risk by situational environments.

OBJECTIVE: Pedestrian-related death rates are increasing in the United States, partly due to increased use of distracting smartphones by pedestrians. Previous research documents high frequency of smartphone use while crossing streets near college campuses and in downtown business districts, but little is known about distracted pedestrian behavior in other urban environments. The current study used observational methods to examine and compare distracted pedestrian behavior in four urban areas - near an urban college campus, in a downtown commercial business district, near middle and high schools, and in entertainment districts - as well as examining whether the occurrence of distraction was associated with unsafe crossing behaviors. METHODS: We observed 112 intersections in 46 downtown, 30 school, 25 entertainment district, and 11 college campus-area intersections. Coders recorded distraction, crossing safety, pedestrian demographics, and traffic volume. Chi-square tests compared pedestrian characteristics by intersection type. Log binomial regressions estimated risk ratios (RRs) and associated 95% confidence intervals (CIs) for associations between pedestrians walking alone and traffic volume with distracted crossing behavior, adjusting for age and gender. Similar models examined risk of unsafe crossing behavior by distraction behavior. All models were stratified by intersection type. RESULTS: Distraction incidence was highest in campus locations (52.9%) and lowest in entertainment districts (16.2%). Walking alone was associated with a 45% higher risk of distraction (RR 1.45, 95% CI 1.30-1.62), although the increased association was limited to entertainment locations (RR 1.61, 95% CI 1.25-2.08) and was significantly decreased in all other locations. Higher traffic volume was associated with lower risk of distraction in downtown locations (RR 0.69, 95% CI 0.56-0.85) but higher distraction risk in entertainment locations (RR 1.71, 95% CI 1.27-2.31). Associations between distraction and unsafe crossing behaviors were minimal. CONCLUSION: Distracted pedestrian behavior occurs at different rates and in different circumstances, depending on the setting. These results offer valuable data to inform intervention programs that target appropriate populations in appropriate locations.

Myeloid Poldip2 Contributes to the Development of Pulmonary Inflammation by Regulating Neutrophil Adhesion in a Murine Model of Acute Respiratory Distress Syndrome.

Background Lung injury, a severe adverse outcome of lipopolysaccharide-induced acute respiratory distress syndrome, is attributed to excessive neutrophil recruitment and effector response. Poldip2 (polymerase δ-interacting protein 2) plays a critical role in regulating endothelial permeability and leukocyte recruitment in acute inflammation. Thus, we hypothesized that myeloid Poldip2 is involved in neutrophil recruitment to inflamed lungs. Methods and Results After characterizing myeloid-specific Poldip2 knockout mice, we showed that at 18 hours post-lipopolysaccharide injection, bronchoalveolar lavage from myeloid Poldip2-deficient mice contained fewer inflammatory cells (8 [4-16] versus 29 [12-57]×104/mL in wild-type mice) and a smaller percentage of neutrophils (30% [28%-34%] versus 38% [33%-41%] in wild-type mice), while the main chemoattractants for neutrophils remained unaffected. In vitro, Poldip2-deficient neutrophils responded as well as wild-type neutrophils to inflammatory stimuli with respect to neutrophil extracellular trap formation, reactive oxygen species production, and induction of cytokines. However, neutrophil adherence to a tumor necrosis factor-α stimulated endothelial monolayer was inhibited by Poldip2 depletion (225 [115-272] wild-type [myePoldip2+/+] versus 133 [62-178] myeloid-specific Poldip2 knockout [myePoldip2-/-] neutrophils) as was transmigration (1.7 [1.3-2.1] versus 1.1 [1.0-1.4] relative to baseline transmigration). To determine the underlying mechanism, we examined the surface expression of ß2-integrin, its binding to soluble intercellular adhesion molecule 1, and Pyk2 phosphorylation. Surface expression of ß2-integrins was not affected by Poldip2 deletion, whereas ß2-integrins and Pyk2 were less activated in Poldip2-deficient neutrophils. Conclusions These results suggest that myeloid Poldip2 is involved in ß2-integrin activation during the inflammatory response, which in turn mediates neutrophil-to-endothelium adhesion in lipopolysaccharide-induced acute respiratory distress syndrome.

Change in craving and frequency of consuming palatable foods for non-homeostatic motives after a gut-cued eating intervention.

INTRODUCTION: Little is known regarding consumption of palatable foods (PFs) for non-homeostatic reasons after weight-loss interventions and if baseline or change in frequency of this kind of eating can predict weight-loss outcomes. Little is also known of the relationship between PF eating for non-homeostatic motives and PF craving. Addressing these gaps is important because cravings and habitual consumption of PFs in the absence of homeostatic need contribute to obesity. METHODS: N = 30 adults with a mean 34.8 BMI completed a seven-response choice version of the PEMS (PEMS-7) before and after Gut-Cued Eating (GCE), an intervention that did not ban PFs but instructed them to eat only when stomach-hungry and stop eating before feeling too full. Photos of PFs were also rated pre- and post-GCE. RESULTS: Frequency of eating PFs for social, reward enhancement, and coping, but not conformity motives, decreased after GCE. The decreases predicted amount of weight loss independent of initial weight and demographics. PF craving also decreased and, while correlated with decreasing PF intake, it did not predict weight loss. DISCUSSION: The study is preliminary because GCE was uncontrolled. However, results warrant a controlled investigation. That craving and frequency of consuming PFs for non-homeostatic motives declined with an intervention that did not ban PFs suggests a method that may voluntarily decrease one's intake of PFs. This should facilitate weight-loss and healthy-weight maintenance. Finally, decreased eating for non-homeostatic motives suggests that individuals were no longer using PFs to cope, socialize, and enhance reward, a change with benefits beyond weight loss.

Associations Between Mother-Child Communication Apprehension, and Young Adult Resilience, Depressive Symptoms, and Self-Esteem.

This study tested associations between mother-child communication apprehension, adult child communication apprehension, and adult child resilience, self-esteem, and depressive symptoms. Data were collected from 154 mother-child dyads (N = 308) who completed measures of communication apprehension, depressive symptoms, resilience, and self-esteem. Results showed that mother communication apprehension positively predicted adult child communication apprehension. Moreover, adult child communication apprehension predicted lower levels of resilience and self-esteem, and higher levels of depressive symptoms. Mother communication apprehension indirectly predicted all three psychological outcomes for adult children through adult children's communication apprehension. We discuss the potential implications for communication apprehension and social skill training that could help families improve psychological problems.

SGK1 signaling promotes glucose metabolism and survival in extracellular matrix detached cells.

Loss of integrin-mediated attachment to extracellular matrix (ECM) proteins can trigger a variety of cellular changes that affect cell viability. Foremost among these is the activation of anoikis, caspase-mediated cell death induced by ECM detachment. In addition, loss of ECM attachment causes profound alterations in cellular metabolism, which can lead to anoikis-independent cell death. Here, we describe a surprising role for serum and glucocorticoid kinase-1 (SGK1) in the promotion of energy production when cells are detached. Our data demonstrate that SGK1 activation is necessary and sufficient for ATP generation during ECM detachment and anchorage-independent growth. More specifically, SGK1 promotes a substantial elevation in glucose uptake because of elevated GLUT1 transcription. In addition, carbon flux into the pentose phosphate pathway (PPP) is necessary to accommodate elevated glucose uptake and PPP-mediated glyceraldehyde-3-phosphate (G3P) is necessary for ATP production. Thus, our data show SGK1 as master regulator of glucose metabolism and cell survival during ECM-detached conditions.

Surveillance for Guillain-Barré syndrome after 2015-2016 and 2016-2017 influenza vaccination of Medicare beneficiaries.

BACKGROUND: Guillain-Barré syndrome (GBS) is a serious acute demyelinating disease, an increased risk of which was found after the 1976 swine flu vaccinations. The U.S. Food and Drug Administration, in collaboration with the Centers for Medicare & Medicaid Services, has been conducting active surveillance for GBS after influenza vaccinations of Medicare Fee-For-Service beneficiaries since 2009. METHODS: We conducted active surveillance for GBS claims in the 2015-2016 and 2016-2017 influenza seasons using the Updating Sequential Probability Ratio Test (USPRT) to monitor for signals of GBS risk. We performed self-controlled risk interval (SCRI) analyses at the end of both seasons, including chart confirmation in the 2015-2016 season, to estimate the odds ratio of GBS risk. We used 1-42 and 8-21 days post-vaccination as primary and secondary risk windows, respectively, and 43-84 days post-vaccination as the control window. RESULTS: Over 13 million beneficiaries were vaccinated in each season. USPRT found a low magnitude signal for GBS in both seasons. SCRI analyses did not find excess GBS risk following any influenza vaccine for days 1-42 post-vaccination in either season. In the 2015-2016 season, for the 8-21 day window, our chart-confirmation showed an attributable GBS risk of 0.87 (95% CI: 0.16, 1.49) and 1.68 (95% CI: 0.69, 2.41) cases per million vaccinees after all seasonal and high dose (HD) vaccines, respectively, an elevated GBS risk for beneficiaries aged ≥75 years following all seasonal vaccines (OR: 2.25; 95% CI: 1.15, 4.39) and HD vaccine (OR: 3.67, 95% CI: 1.52, 8.85), and an elevated GBS risk for males who received seasonal vaccines (OR: 2.18; 95% CI: 1.15, 4.15) and HD vaccine (OR: 3.33; 95% CI: 1.35, 8.20). The finding of elevated GBS risk with advancing age and in males is consistent with literature; however, a distinction between HD and SD was a new finding. In the 2016-17 season, for the 8-21 day window, attributed cases showed an attributable GBS risk of 0.87 (95% CI: 0.03, 1.61) and 1.11 (95% CI: 0.00, 2.01) cases per million vaccinees after all seasonal and HD vaccines, respectively. We found no excess GBS risk for standard dose vaccines in the 8-21 day window in either season. CONCLUSIONS: Our primary analysis finding of no excess GBS risk during both seasons was reassuring. The slightly elevated GBS risk, although in the expected range, in the 8-21 day window after all seasonal and high dose vaccines, but not after standard dose vaccines is hypothesis-generating because the difference may be due to vaccine factors such as antigen amount or strains in various seasons or due to host factors.

Patient perspectives on compensation for biospecimen donation.

BACKGROUND: The purpose of this study was to determine whether biospecimen donors believe they should receive compensation. This is the first study to report biospecimen donors' views on compensation and can potentially improve informed consent and recruitment practices. METHODS: Researchers asked patients undergoing surgical removal of tissue to donate biological materials to a biobank; the request was made at their presurgical appointment or in the preoperative clinic of the Emory University Hospital. We interviewed 126 biospecimen donors within 30 days post surgery regarding their perspective on compensation for biospecimen donation. RESULTS: In response to the question "Should you be paid for your participation in the tissue bank?," 95 (95/126, 75%) participants answered "No." Of these, 55 (55/95, 58%) indicated that donating biological materials should be about altruism, not gaining a monetary reward. Only 11 (11/126, 9%) participants unequivocally believed they should receive compensation, while 14 (14/126, 11%) felt entitled to compensation only under specific circumstances. Eleven (11/14) "Depends" participants indicated that donors should only be compensated when researchers perform for-profit research. Responses varied by race and income level, with whites more likely to not feel entitled to compensation and higher income participants more likely to respond "Depends." CONCLUSIONS: The majority of biospecimen donors stated they should not be paid for tissue bank participation. However, a minority believe they should be paid for donating tissue if the tissue is used in revenue-generating projects. These results provide some support for the current biobanking practice of not providing compensation.

Providing Comprehensive Medication Management in Telehealth.

The goal of this white paper is to provide direction for clinical pharmacists providing telehealth. Telehealth care is rapidly emerging to improve patient access to health care and optimize patient health outcomes. With the increasing ability to access electronic health record portals, as many as 75 million telehealth encounters are expected in North America annually. Although electronic "point of access" undoubtedly increases the use of medical and pharmacy services, the real value of telehealth lies in improved access to patients in remote areas lacking adequate medical and pharmacy services and to high-risk patients requiring frequent monitoring. This document is intended to serve as a guide for those interested in or already using telehealth to provide direct patient care. Specifically, it focuses on general concepts of telehealth and demonstrates how the delivery of comprehensive medication management (CMM) by telehealth aligns with the Standards of Practice for Clinical Pharmacists set forth by the American College of Clinical Pharmacy. Although clinical pharmacists must be appropriately credentialed and privileged to provide CMM, their process of care must also be adapted to suit the remote patient. Patient assessment, evaluation of medication therapy, development and implementation of a plan of care, follow-up, monitoring, and documentation of all processes of care are influenced by the technology available, the collaborations established, and the applicable regulations and requirements for telehealth practice.

Family Strategies to Support Siblings of Pediatric Hematopoietic Stem Cell Transplant Patients.

OBJECTIVE: To describe the strategies families report using to address the needs and concerns of siblings of children, adolescents, and young adults undergoing hematopoietic stem cell transplant (HSCT). METHODS: A secondary semantic analysis was conducted of 86 qualitative interviews with family members of children, adolescents, and young adults undergoing HSCT at 4 HSCT centers and supplemented with a primary analysis of 38 additional targeted qualitative interviews (23 family members, 15 health care professionals) conducted at the primary center. Analyses focused on sibling issues and the strategies families use to address these issues. RESULTS: The sibling issues identified included: (1) feeling negative effects of separation from the patient and caregiver(s); (2) experiencing difficult emotions; (3) being faced with additional responsibilities or burdens; (4) lacking information; and (5) feeling excluded. Families and health care providers reported the following strategies to support siblings: (1) sharing information; (2) using social support and help offered by family or friends; (3) taking siblings to the hospital; (4) communicating virtually; (5) providing special events or gifts or quality time for siblings; (6) offering siblings a defined role to help the family during the transplant process; (7) switching between parents at the hospital; (8) keeping the sibling's life constant; and, (9) arranging sibling meetings with a certified child life specialist or school counselor. CONCLUSIONS: Understanding the above strategies and sharing them with other families in similar situations can begin to address sibling issues during HSCT and can improve hospital-based, family-centered care efforts.

A sensitive high performance liquid chromatography assay for the quantification of doxorubicin associated with DNA in tumor and tissues.

Doxorubicin, a widely used anticancer agent, exhibits antitumor activity against a wide variety of malignancies. The drug exerts its cytotoxic effects by binding to and intercalating within the DNA of tumor and tissue cells. However, current assays are unable to accurately determine the concentration of the intracellular active form of doxorubicin. Thus, the development of a sample processing method and a high-performance liquid chromatography (HPLC) methodology was performed in order to quantify doxorubicin that is associated with DNA in tumors and tissues, which provided an intracellular cytotoxic measure of doxorubicin exposure after administration of small molecule and nanoparticle formulations of doxorubicin. The assay uses daunorubicin as an internal standard; liquid-liquid phase extraction to isolate drug associated with DNA; a Shimadzu HPLC with fluorescence detection equipped with a Phenomenex Luna C18 (2µm, 2.0×100mm) analytical column and a gradient mobile phase of 0.1% formic acid in water or acetonitrile for separation and quantification. The assay has a lower limit of detection (LLOQ) of 10ng/mL and is shown to be linear up to 3000ng/mL. The intra- and inter-day precision of the assay expressed as a coefficient of variation (CV%) ranged from 4.01 to 8.81%. Furthermore, the suitability of this assay for measuring doxorubicin associated with DNA in vivo was demonstrated by using it to quantify the doxorubicin concentration within tumor samples from SKOV3 and HEC1A mice obtained 72h after administration of PEGylated liposomal doxorubicin (Doxil(®); PLD) at 6mg/kg IV x 1. This HPLC assay allows for sensitive intracellular quantification of doxorubicin and will be an important tool for future studies evaluating intracellular pharmacokinetics of doxorubicin and various nanoparticle formulations of doxorubicin.

Step counts of non-white minority children and youth by gender, grade level, race/ethnicity, and mode of school transportation.

BACKGROUND: The purposes of this study were to describe and analyze the steps/d of nonwhite minority children and youth by gender, grade level, race/ethnicity, and mode of school transportation. A secondary purpose was to compare the steps/d of minority children and youth to their Caucasian grade-level counterparts. METHODS: Participants were 547 minority youth grades 5 to 8 from 4 urban schools. Participants wore sealed pedometers for 6 consecutive week/school days. Three hundred and ten participants responded to a questionnaire concerning their mode of transportation to and from school. RESULTS: Statistical analyses indicated a main effect for gender (F(3, 546) = 13.50, P < .001) with no interaction. Boys (12,589 ± 3921) accumulated significantly more steps/d than girls (9,539 ± 3,135). Further analyses also revealed a significant main effect for mode of school transportation (F(2, 309) = 15.97, P ≤ .001). Walkers (12,614 ± 4169) obtained significantly more steps/d than car (10,021 ± 2856) or bus (10,230 ± 3666) transit users. CONCLUSIONS: Minority boys obtain similar steps/d as their Caucasian grade-level counterparts; minority girls obtain less steps/d than their Caucasian grade-level counterparts. Minority youth who actively commute are more likely to meet PA recommendations than nonactive commuters.

Development of a measure of willingness to provide nursing care to AIDS patients.

The Nursing Willingness Questionnaire (NWQ) was developed to measure nurses' willingness to perform specific direct care activities for an adult male patient with acquired immunodeficiency syndrome (AIDS). Measures of internal consistency and one-week test-retest stability indicated excellent reliability. NWQ scale scores correlated significantly with a measure of fear of contracting AIDS via interpersonal and medical contacts but not with fear of contagion through risky sexual behavior. In principle components analysis, all items loaded on one factor. These psychometric studies suggest the NWQ is a reliable and valid instrument for evaluating a construct of current concern to nursing administrators and educators.