Knowledge and perceptions of human trafficking among community-based and faith-based organization members in South Los Angeles.

The objectives of this study were (1) to assess the knowledge and perceptions of human trafficking (HT) among leaders and staff from 11 community-based organizations (CBOs) and faith-based organizations (FBOs) in South Los Angeles, and (2) to identify gaps in knowledge of HT and inform community organizations regarding possible best practices in health promotion for addressing this emerging public health problem. A self-administered survey was conducted during the period from 4 December 2015 to 28 January 2016. Descriptive statistics were generated and a logistic regression model was constructed using SAS 9.3. A total of 277 CBO and FBO leaders and staff completed the survey. Participants demonstrated high levels of knowledge of HT but their knowledge was not comprehensive, as gaps exist in recognizing the context in which HT usually takes place; understanding the local laws that govern this activity; and ways to follow related policies/procedures when the problem is suspected. A majority (a) believed there were not enough services in Los Angeles County to help survivors of HT, (b) could not recognize the signs of HT, and (c) did not know what steps to take if they suspected this criminal activity. A statistically significant association was found between education and participants' knowledge of HT, and with their beliefs and attitudes toward this violation of human rights. Study findings suggest that, generally, CBO/FBO leaders and staff in South Los Angeles have good knowledge about HT. However, notable gaps in knowledge and misperceptions remain, suggesting opportunities for Public Health to further educate and intervene.

Structure-Activity Relationships of 7-Substituted Dimethyltyrosine-Tetrahydroisoquinoline Opioid Peptidomimetics.

The opioid receptors modulate a variety of biological functions, including pain, mood, and reward. As a result, opioid ligands are being explored as potential therapeutics for a variety of indications. Multifunctional opioid ligands, which act simultaneously at more than one type of opioid receptor, show promise for use in the treatment of addiction, pain, and other conditions. Previously, we reported the creation of bifunctional kappa opioid receptor (KOR) agonist/mu opioid receptor (MOR) partial agonist ligands from the classically delta opioid receptor (DOR) antagonist selective dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold through the addition of a 7-benzyl pendant on the tetrahydroisoquinoline ring. This study further explores the structure-activity relationships surrounding 7-position pendants on the Dmt-Tiq scaffold. Some analogues maintain a KOR agonist/MOR partial agonist profile, which is being explored in the development of a treatment for cocaine addiction. Others display a MOR agonist/DOR antagonist profile, which has potential to be used in the creation of a less addictive pain medication. Ultimately, we report the synthesis and in vitro evaluation of novel opioid ligands with a variety of multifunctional profiles.

Novel Dimethyltyrosine-Tetrahydroisoquinoline Peptidomimetics with Aromatic Tetrahydroisoquinoline Substitutions Show in Vitro Kappa and Mu Opioid Receptor Agonism.

The dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold was originally developed in the production of selective delta opioid receptor (DOR) antagonists. Installation of a 7-benzyl pendant on the tetrahydroisoquinoline core of this classic opioid scaffold introduced kappa opioid receptor (KOR) agonism. Further modification of this pendant resulted in retention of KOR agonism and the addition of mu opioid receptor (MOR) partial agonism, a bifunctional profile with potential to be used in the treatment of cocaine addiction.

Dual Pharmacophores Explored via Structure-Activity Relationship (SAR) Matrix: Insights into Potent, Bifunctional Opioid Ligand Design.

Short-acting µ-opioid receptor (MOR) agonists have long been used for the treatment of severe, breakthrough pain. However, selective MOR agonists including fentanyl and morphine derivatives are limited clinically due to high risks of dependence, tolerance, and respiratory depression. We recently reported the development of a long-acting, bifunctional MOR agonist/δ-opioid receptor (DOR) antagonist analgesic devoid of tolerance or dependence in mice (AAH8, henceforth referred to as 2B). To address the need for short-acting treatments for breakthrough pain, we present a series of novel, short-acting, high-potency MOR agonist/DOR antagonist ligands with antinociceptive activity in vivo. In this study, we utilized a two-dimensional structure-activity relationship matrix to identify pharmacological trends attributable to combinations of two key pharmacophore elements within the chemotype. This work enhances our ability to modulate efficacy at MOR and DOR, accessing a variety of bifunctional profiles while maintaining high affinity and potency at both receptors.

Multifunctional Opioid Ligands.

The opioid receptor system plays a major role in the regulation of mood, reward, and pain. The opioid receptors therefore make attractive targets for the treatment of many different conditions, including pain, depression, and addiction. However, stimulation or blockade of any one opioid receptor type often leads to on-target adverse effects that limit the clinical utility of a selective opioid agonist or antagonist. Literature precedent suggests that the opioid receptors do not act in isolation and that interactions among the opioid receptors and between the opioid receptors and other proteins may produce clinically useful targets. Multifunctional ligands have the potential to elicit desired outcomes with reduced adverse effects by allowing for the activation of specific receptor conformations and/or signaling pathways promoted as a result of receptor oligomerization or crosstalk. In this chapter, we describe several classes of multifunctional ligands that interact with at least one opioid receptor. These ligands have been designed for biochemical exploration and the treatment of a wide variety of conditions, including multiple kinds of pain, depression, anxiety, addiction, and gastrointestinal disorders. The structures, pharmacological utility, and therapeutic drawbacks of these classes of ligands are discussed.

In vivo effects of µ-opioid receptor agonist/δ-opioid receptor antagonist peptidomimetics following acute and repeated administration.

BACKGROUND AND PURPOSE: Agonists at µ-opioid receptors (µ-receptors) are used for pain management but produce adverse effects including tolerance, dependence and euphoria. The co-administration of a µ-receptor agonist with a δ-opioid receptor (δ-receptor) antagonist has been shown to produce antinociception with reduced development of some side effects. We characterized the effects of three µ-receptor agonist/δ-receptor antagonist peptidomimetics in vivo after acute and repeated administration to determine if this profile provides a viable alternative to traditional opioid analgesics. EXPERIMENTAL APPROACH: Three µ-receptor agonist / δ-receptor antagonist peptidomimetics, AAH8, AMB46 and AMB47, and morphine were evaluated for the development of tolerance and dependence after 5 days of twice daily treatment with escalating doses of drug (10-50 mg·kg-1 ). Antinociceptive effects were measured in the warm water tail withdrawal assay before and after repeated drug treatment. Physical dependence was evaluated by naltrexone-precipitated withdrawal jumping. The rewarding effects of AAH8 were evaluated using a conditioned place preference (CPP) assay with twice daily conditioning sessions performed for 5 days. KEY RESULTS: Morphine, AAH8, AMB47 and AMB46 all demonstrated acute antinociceptive effects, but repeated administration only produced tolerance in animals treated with morphine and AMB46. Injection of naltrexone precipitated fewer jumps in mice treated repeatedly with AAH8 as compared with morphine, AMB47 or AMB46. Conditioning with morphine, but not AAH8, produced significant CPP. CONCLUSIONS AND IMPLICATIONS: AAH8 may be a better alternative than traditional opioid analgesics, producing antinociception with less development of tolerance and dependence and may be less rewarding than morphine.

Community-based Flu Outreach Clinics in South Los Angeles: Client Satisfaction and Experiences.

OBJECTIVE: This study sought to better understand and improve influenza vaccination in low-income populations regardless of their health insurance/immigration status. It assessed client satisfaction and experiences with services provided at community-based "flu outreach" clinics in South Los Angeles. The clinics represent a community-public agency partnership-a model of vaccine delivery that was relatively novel to the region. DESIGN AND SAMPLE: During 2011-2012, a self-administered questionnaire was distributed to clients of the local health department's 39 flu outreach clinics in South Los Angeles. MEASURES: The study utilized a 10-item satisfaction scale and survey questions that gauged client history and experiences with present and prior vaccinations. RESULTS: Of 4,497 adults who were eligible, 3,860 completed the survey (participation rate = 86%). More than 90% were satisfied with their experiences at the clinics. Younger adults were significantly more likely than adults aged 65+ to report not having been vaccinated in the previous year (p < .05). No statistical differences were observed by gender or race/ethnicity. CONCLUSIONS: High satisfaction with flu outreach services in South Los Angeles suggests that this model for vaccine delivery could lead to meaningful client experience of care. Local health departments could capitalize on this model to improve preventive services delivery for the underserved.

Constrained bithiazoles: small molecule correctors of defective ΔF508-CFTR protein trafficking.

Conformationally constrained bithiazoles were previously found to have improved efficacy over nonconstrained bithiazoles for correction of defective cellular processing of the ΔF508 mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. In this study, two sets of constrained bithiazoles were designed, synthesized, and tested in vitro using ΔF508-CFTR expressing epithelial cells. The SAR data demonstrated that modulating the constraining ring size between 7- versus 8-membered in these constrained bithiazole correctors did not significantly enhance their potency (IC50), but strongly affected maximum efficacy (Vmax), with constrained bithiazoles 9e and 10c increasing Vmax by 1.5-fold compared to benchmark bithiazole corr4a. The data suggest that the 7- and 8-membered constrained ring bithiazoles are similar in their ability to accommodate the requisite geometric constraints during protein binding.

Nutrient Intakes of Third Graders: Results from the Child and Adolescent Trial for Cardiovascular Health (CATCH) Baseline Survey.

The purpose of this article is to report on baseline intakes of 1874 third-grade children representing a subsample of the Child and Adolescent Trial for Cardiovascular Health (CATCH) cohort. Intakes were assessed using a single, food record-assisted, 24-hour recall. The sample is unique in that it is drawn from four states and includes students from various ethnic backgrounds. Nutrients of interest include total energy, sodium, dietary cholesterol, and percent of energy from total fat and saturated fat. At baseline, third-grade students were consuming above nationally recommended levels of energy from fat, saturated fat, and sodium. The CATCH findings show a mean energy intake of 2031 kcal with significant differences by sex. Significant differences by site were seen for percent of energy from total fat, saturated fat, and dietary cholesterol. Children from Minnesota consumed the lowest proportion of energy from total fat and saturated fat while children from Texas had the highest proportion of energy from total fat and saturated fat. Intake of dietary cholesterol was lowest in Minnesota and highest in Louisiana. Nutrient differences by ethnic group were seen only for energy, with African Americans having the highest energy intake and Hispanics having the lowest energy intake. The number of meals consumed from school food service significantly influenced children's nutrient, intake; children consuming two meals from school food service had significantly greater intakes of energy, saturated fat, and dietary cholesterol compared to students consuming one or no meals from school food-service. The results are compared to other national nutritional surveys of children.