Modulation of the multidrug efflux pump EmrD-3 from Vibrio cholerae by Allium sativum extract and the bioactive agent allyl sulfide plus synergistic enhancement of antimicrobial susceptibility by A. sativum extract.

The causative agent of cholera, Vibrio cholerae, is a public health concern. Multidrug-resistant V. cholerae variants may reduce chemotherapeutic efficacies of severe cholera. We previously reported that the multidrug efflux pump EmrD-3 from V. cholerae confers resistance to multiple structurally distinct antimicrobials. Medicinal plant compounds are potential candidates for EmrD-3 efflux pump modulation. The antibacterial activities of garlic Allium sativum, although poorly understood, predicts that a main bioactive component, allyl sulfide, modulates EmrD-3 efflux. Thus, we tested whether A. sativum extract acts in synergy with antimicrobials and that a main bioactive component allyl sulfide inhibits EmrD-3 efflux. We found that A. sativum extract and allyl sulfide inhibited ethidium bromide efflux in cells harboring EmrD-3 and that A. sativum lowered the MICs of multiple antibacterials. We conclude that A. sativum and allyl sulfide inhibit EmrD-3 and that A. sativum extract synergistically enhances antibacterial agents.

Feasibility and Effects of a Neuromuscular Warm-Up Based on the Physical Literacy Model for 8-12-Year-Old-Children.

Background: Physical literacy and injury prevention strategies use similar movement-related constructs and can be connected to develop comprehensive interventions. We aimed to test the feasibility and effects of a neuromuscular warm-up based on physical literacy and injury prevention strategies for 8-12-year-old children. Methods: We conducted a cluster non-randomized controlled trial. We defined a priori feasibility criteria and studied the effects of the intervention on physical literacy constructs, movement competence, and neuromuscular performance. We used generalized linear mixed models controlling for covariates and clustering with a significance level of 0.001. Results: We recruited 18 groups (n = 363) and randomly allocated nine to intervention (n = 179; female = 63.7%, age = 9.8 ± 1 years) and nine to control (n = 184, female = 53.3%, age = 9.9 ± 0.9 years). We met four of seven feasibility criteria (i.e. recruitment, adherence, enjoyment, perceived exertion). The three feasibility criteria that were not met (i.e. compliance, fidelity, follow-up) were slightly below the predefined threshold (90%). Model-adjusted mean differences for physical literacy constructs, movement competence, vertical jump height, horizontal jump distance, 20-m sprint time, and dynamic balance favored the intervention (p < .001). Conclusion: The feasibility evidence indicates that the intervention should be slightly modified before implementing it in a larger study. The observed mean differences are promising and can be used in planning future interventions.

Social marketing and the challenges of participant recruitment.

Recruitment of research participants often has not obtained a desired sample size, thereby becoming a major problem inhibiting investigators' ability to adequately test the specified hypotheses. Social marketing with its four Ps, originally developed by the business world to sell products and adapted for public health initiatives, is proposed as a dynamic comprehensive conceptual framework to apply marketing principles and practices to enhance participant recruitment. Applying a social marketing approach to research recruitment would require initial investigation to understand the motivations of the target audience in regard to research participation, and continued research throughout the main project to adapt the recruitment efforts as limitations arise. Additional funding would be needed for successful social marketing research recruitment programs to be systematically implemented and evaluated as part of research projects. In this paper, we define social marketing concepts, briefly review the available literature supporting social marketing applied to recruitment for research studies, and consider ethical issues that may arise when using a social marketing approach.

Recruitment for research projects has been challenging, putting studies at risk of not being able to adequately test a priori hypotheses. Social marketing, an adaptation of traditional marketing principles and practices, may provide a solution. Marketing was developed to sell commercial products to consumers, and the strategies and practices therein could be applied to selling participation in the "intervention" (the health program) to "end users" (participants). The four Ps, product, price, place, and promotion, are the conceptual elements considered in a marketing plan. Applying a social marketing approach to recruitment for research projects has been demonstrated to be successful in a small number of cases. Implementing this approach would require preimplementation research to specify the key characteristics of the target audience; continuous monitoring of recruitment success during the research to assess changes in strategies, as needed; and enhanced funding to accommodate the additional research within an expanded early project time frame.

Effects of Multicomponent Injury Prevention Programs on Children and Adolescents' Fundamental Movement Skills: A Systematic Review With Meta-Analyses.

OBJECTIVE: Fundamental movement skills (FMS) are essential to participate in physical activity. Understanding the effects of multicomponent injury prevention programs (MIPP) on FMS may help promote safe physical activity. Our objective was to synthesize the evidence on the effects of MIPP on biomechanical outcomes and neuromuscular performance measured on children and adolescents while performing FMS. DATA SOURCE: We searched PubMed, SPORTDiscus, Web of Science, and SCOPUS. STUDY INCLUSION AND EXCLUSION CRITERIA: We included peer-reviewed randomized controlled trials, published in English, that analyzed the effects of MIPP on biomechanics and neuromuscular performance of FMS in participants under 18 years of age. DATA EXTRACTION: Two reviewers screened the articles, assessed the quality of the evidence using the Physiotherapy Evidence Database (PEDro) scale, and synthesized the data. DATA SYNTHESIS: We conducted meta-analyses and reported the characteristics, outcomes, and risk of bias of studies. RESULTS: We included 27 articles that reported data from 1,427 participants. Positive effects on FMS were reported in 23 of the 27 included articles. Vertical Jump, running speed, acceleration, and dynamic balance presented positive-significant pooled effect sizes. Dribbling and horizontal jump presented non-significant pooled effect sizes. CONCLUSION: MIPP can positively affect FMS in children and adolescents in sports-related settings. Lack of participant compliance and implementation fidelity may affect MIPP effectiveness. Including MIPP in physical literacy interventions, physical education classes, and organized physical activity may lead to functional adaptations that help promote safe physical activity.

Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial.

BACKGROUND: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma virus (HPV)-associated OPC and long-term survival of these typically young patients, treatment de-intensification aimed at improving survivorship while maintaining excellent disease control is now a central concern. The recent implementation of magnetic resonance image - guided radiotherapy (MRgRT) systems allows for individual tumor response assessment during treatment and offers possibility of personalized dose-reduction. In this 2-stage Bayesian phase II study, we propose to examine weekly radiotherapy dose-adaptation based on magnetic resonance imaging (MRI) evaluated tumor response. Individual patient's plan will be designed to optimize dose reduction to organs at risk and minimize locoregional failure probability based on serial MRI during RT. Our primary aim is to assess the non-inferiority of MRgRT dose adaptation for patients with low risk HPV-associated OPC compared to historical control, as measured by Bayesian posterior probability of locoregional control (LRC). METHODS: Patients with T1-2 N0-2b (as per AJCC 7th Edition) HPV-positive OPC, with lymph node <3 cm and <10 pack-year smoking history planned for curative radiotherapy alone to a dose of 70 Gy in 33 fractions will be eligible. All patients will undergo pre-treatment MRI and at least weekly intra-treatment MRI. Patients undergoing MRgRT will have weekly adaptation of high dose planning target volume based on gross tumor volume response. The stage 1 of this study will enroll 15 patients to MRgRT dose adaptation. If LRC at 6 months with MRgRT dose adaptation is found sufficiently safe as per the Bayesian model, stage 2 of the protocol will expand enrollment to an additional 60 patients, randomized to either MRgRT or standard IMRT. DISCUSSION: Multiple methods for safe treatment de-escalation in patients with HPV-positive OPC are currently being studied. By leveraging the ability of advanced MRI techniques to visualize tumor and soft tissues through the course of treatment, this protocol proposes a workflow for safe personalized radiation dose-reduction in good responders with radiosensitive tumors, while ensuring tumoricidal dose to more radioresistant tumors. MRgRT dose adaptation could translate in reduced long term radiation toxicities and improved survivorship while maintaining excellent LRC outcomes in favorable OPC. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03224000; Registration date: 07/21/2017.

Latina/o or Mexicana/o?: The Relationship between Socially Assigned Race and Experiences with Discrimination.

Discrimination based on one's racial or ethnic background is one of the oldest and most perverse practices in the United States. While much of this research has relied on self-reported racial categories, a growing body of research is attempting to measure race through socially-assigned race. Socially-assigned or ascribed race measures how individuals feel they are classified by other people. This paper draws on the socially assigned race literature and explores the impact of socially assigned race on experiences with discrimination using a 2011 nationally representative sample of Latina/os (n=1,200). While much of the current research on Latina/os has been focused on the aggregation across national origin group members, this paper marks a deviation by using socially-assigned race and national origin to understand how being ascribed as Mexican is associated with experiences of discrimination. We find evidence that being ascribed as Mexican increases the likelihood of experiencing discrimination relative to being ascribed as White or Latina/o. Furthermore, we find that being miss-classified as Mexican (ascribed as Mexican, but not of Mexican origin) is associated with a higher likelihood of experiencing discrimination compared to being ascribed as white, ascribed as Latina/o, and correctly ascribed as Mexican. We provide evidence that socially assigned race is a valuable complement to self-identified race/ethnicity for scholars interested in assessing the impact of race/ethnicity on a wide range of outcomes.

RACE AS LIVED EXPERIENCE: The Impact of Multi-Dimensional Measures of Race/Ethnicity on the Self-Reported Health Status of Latinos.

A growing body of social science research has sought to conceptualize race as a multidimensional concept in which context, societal relations, and institutional dynamics are key components. Utilizing a specially designed survey, we develop and use multiple measures of race (skin color, ascribed race, and discrimination experiences) to capture race as "lived experience" and assess their impact on Latinos' self-rated health status. We model these measures of race as a lived experience to test the explanatory power of race, both independently and as an integrated scale with categorical regression, scaling, and dimensional analyses. Our analyses show that our multiple measures of race have significant and negative effects on Latinos' self-reported health. Skin color is a dominant factor that impacts self-reported health both directly and indirectly. We then advocate for the utilization of multiple measures of race, adding to those used in our analysis, and their application to other health and social outcomes. Our analysis provides important contributions across a wide range of health, illness, social, and political outcomes for communities of color.

Proton versus conventional radiotherapy for pediatric salivary gland tumors: Acute toxicity and dosimetric characteristics.

PURPOSE: We evaluated acute toxicity profiles and dosimetric data for children with salivary gland tumors treated with adjuvant photon/electron-based radiation therapy (X/E RT) or proton therapy (PRT). METHODS AND MATERIALS: We identified 24 patients who had received adjuvant radiotherapy for salivary gland tumors. Data were extracted from the medical records and the treatment planning systems. Toxicity was scored according to the Common Terminology Criteria for Adverse Effects 4.0. RESULTS: Eleven patients received X/E RT and 13 PRT, with a median prescribed dose of 60 Gy in each group. In the X/E RT group, 54% of patients developed acute grade II/III dermatitis, 27% grade II/III dysphagia, and 91% grade II/III mucositis, and the median weight loss was 5.3% with one patient requiring feeding tube placement. In the PRT group, 53% had acute grade II/III dermatitis, 0% grade II/III dysphagia, and 46% grade II/III mucositis, with a median weight gain of 1.2%. Additionally, PRT was associated with lower mean doses to several normal surrounding midline and contralateral structures. CONCLUSION: In this retrospective study of pediatric salivary tumors, PRT was associated with a favorable acute toxicity and dosimetric profile. Continued follow-up is needed to identify long-term toxicity and survival data.

Incidence and predictors of Lhermitte's sign among patients receiving mediastinal radiation for lymphoma.

PURPOSE: To prospectively examine the risk of developing Lhermitte's sign (LS) in patients with lymphoma treated with modern-era chemotherapy followed by consolidation intensity-modulated radiation therapy. METHODS: We prospectively interviewed all patients with lymphoma who received irradiation to the mediastinum from July 2011 through April 2014. We extracted patient, disease, and treatment-related variables from the medical records of those patients and dosimetric variables from treatment-planning systems and analyzed these factors to identify potential predictors of LS with Pearson chi-square tests. RESULTS: During the study period 106 patients received mediastinal radiation for lymphoma, and 31 (29 %) developed LS. No correlations were found between LS and any of the variables examined, including total radiation dose, maximum point dose to the spinal cord, volume receiving 105 % of the dose, and volumes receiving 5 or 15 Gy. CONCLUSION: In this group of patients, treatment with chemotherapy followed by intensity-modulated radiation therapy led to 29 % developing LS; this symptom was independent of radiation dose and seemed to be an idiosyncratic reaction. This relatively high incidence could have resulted from prospective use of a structured interview.

Spot-scanning beam proton therapy vs intensity-modulated radiation therapy for ipsilateral head and neck malignancies: a treatment planning comparison.

Radiation therapy for head and neck malignancies can have side effects that impede quality of life. Theoretically, proton therapy can reduce treatment-related morbidity by minimizing the dose to critical normal tissues. We evaluated the feasibility of spot-scanning proton therapy for head and neck malignancies and compared dosimetry between those plans and intensity-modulated radiation therapy (IMRT) plans. Plans from 5 patients who had undergone IMRT for primary tumors of the head and neck were used for planning proton therapy. Both sets of plans were prepared using computed tomography (CT) scans with the goals of achieving 100% of the prescribed dose to the clinical target volume (CTV) and 95% to the planning TV (PTV) while maximizing conformity to the PTV. Dose-volume histograms were generated and compared, as were conformity indexes (CIs) to the PTVs and mean doses to the organs at risk (OARs). Both modalities in all cases achieved 100% of the dose to the CTV and 95% to the PTV. Mean PTV CIs were comparable (0.371 IMRT, 0.374 protons, p = 0.953). Mean doses were significantly lower in the proton plans to the contralateral submandibular (638.7 cGy IMRT, 4.3 cGy protons, p = 0.002) and parotid (533.3 cGy IMRT, 48.5 cGy protons, p = 0.003) glands; oral cavity (1760.4 cGy IMRT, 458.9 cGy protons, p = 0.003); spinal cord (2112.4 cGy IMRT, 249.2 cGy protons, p = 0.002); and brainstem (1553.52 cGy IMRT, 166.2 cGy protons, p = 0.005). Proton plans also produced lower maximum doses to the spinal cord (3692.1 cGy IMRT, 2014.8 cGy protons, p = 0.034) and brainstem (3412.1 cGy IMRT, 1387.6 cGy protons, p = 0.005). Normal tissue V10, V30, and V50 values were also significantly lower in the proton plans. We conclude that spot-scanning proton therapy can significantly reduce the integral dose to head and neck critical structures. Prospective studies are underway to determine if this reduced dose translates to improved quality of life.

Adaptive radiotherapy for head and neck cancer--dosimetric results from a prospective clinical trial.

PURPOSE: To conduct a clinical trial evaluating adaptive head and neck radiotherapy (ART). METHODS: Patients with locally advanced oropharyngeal cancer were prospectively enrolled. Daily CT-guided setup and deformable image registration permitted mapping of dose to avoidance structures and CTVs. We compared four planning scenarios: (1) original IMRT plan aligned daily to marked isocenter (BB); (2) original plan aligned daily to bone (IGRT); (3) IGRT with one adaptive replan (ART1); and (4) actual treatment received by each study patient (IGRT with one or two adaptive replans, ART2). RESULTS: All 22 study patients underwent one replan (ART1); eight patients had two replans (ART2). ART1 reduced mean dose to contralateral parotid by 0.6 Gy or 2.8% (paired t-test; p=0.003) and ipsilateral parotid by 1.3 Gy (3.9%) (p=0.002) over the IGRT alone. ART2 further reduced the mean contralateral parotid dose by 0.8 Gy or 3.8% (p=0.026) and ipsilateral parotid by 4.1 Gy or 9% (p=0.001). ART significantly reduced integral body dose. CONCLUSIONS: This pilot trial suggests that head and neck ART dosimetrically outperforms IMRT. IGRT that leverages conventional PTV margins does not improve dosimetry. One properly timed replan delivers the majority of achievable dosimetric improvement. The clinical impact of ART must be confirmed by future trials.

Rationale for and preliminary results of proton beam therapy for mediastinal lymphoma.

PURPOSE: To evaluate the potential of three-dimensional proton beam therapy (3D-PBT) for reducing doses to normal structures in patients with mediastinal lymphomas compared with conventional photon radiation therapy (RT). METHODS AND MATERIALS: We treated 10 consecutive patients with mediastinal masses from lymphomas with 3D-PBT between July 2007 and February 2009 to 30.6-50.4 cobalt-Gray equivalents (CGE). Of those patients, 7 had primary refractory or recurrent disease, and 8 had Hodgkin lymphoma. Dosimetric endpoints were compared with those from conventional RT plans. RESULTS: PBT delivered lower mean doses to the lung (6.2 vs. 9.5 Gy), esophagus (9.5 vs. 22.3 Gy), and heart (8.8 vs. 17.7 Gy) but not the breasts (5.9 vs. 6.1 Gy) than did conventional RT. Percentages of lung, esophagus, heart, and coronary artery (particularly the left anterior descending artery) volumes receiving radiation were consistently lower in the 3D-PBT plans over a wide range of radiation doses. Of the 7 patients who had residual disease on positron emission tomography before PBT, 6 (86%) showed a complete metabolic response. CONCLUSIONS: In patients with mediastinal lymphomas, 3D-PBT produced significantly lower doses to the lung, esophagus, heart, and coronary arteries than did the current conventional RT. These lower doses would be expected to reduce the risk of late toxicities in these major organs.

Simple carotid-sparing intensity-modulated radiotherapy technique and preliminary experience for T1-2 glottic cancer.

PURPOSE: To investigate the dosimetry and feasibility of carotid-sparing intensity-modulated radiotherapy (IMRT) for early glottic cancer and to report preliminary clinical experience. METHODS AND MATERIALS: Digital Imaging and Communications in Medicine radiotherapy (DICOM-RT) datasets from 6 T1-2 conventionally treated glottic cancer patients were used to create both conventional IMRT plans. We developed a simplified IMRT planning algorithm with three fields and limited segments. Conventional and IMRT plans were compared using generalized equivalent uniform dose and dose-volume parameters for in-field carotid arteries, target volumes, and organs at risk. We have treated 11 patients with this simplified IMRT technique. RESULTS: Intensity-modulated radiotherapy consistently reduced radiation dose to the carotid arteries (p < 0.05) while maintaining the clinical target volume coverage. With conventional planning, median carotid V35, V50, and V63 were 100%, 100%, and 69.0%, respectively. With IMRT planning these decreased to 2%, 0%, and 0%, respectively (p < 0.01). Radiation planning and treatment times were similar for conventional radiotherapy and IMRT. Treatment results have been excellent thus far. CONCLUSIONS: Intensity-modulated radiotherapy significantly reduced unnecessary radiation dose to the carotid arteries compared with conventional lateral fields while maintaining clinical target volume coverage. Further experience and longer follow-up will be required to demonstrate outcomes for cancer control and carotid artery effects.