Antigen stasis and airway nitrosative stress in human primary ciliary dyskinesia.

Nasal nitric oxide (nNO) is low in most patients with primary ciliary dyskinesia (PCD). Decreased ciliary motion could lead to antigen stasis, increasing oxidant production and NO oxidation in the airways. This could both decrease gas phase NO and increase nitrosative stress. We studied primary airway epithelial cells from healthy controls (HCs) and patients with PCD with several different genotypes. We measured antigen clearance in fenestrated membranes exposed apically to the fluorescently labeled antigen Dermatophagoides pteronyssinus (Derp1-f). We immunoblotted for 3-nitrotyrosine (3-NT) and for oxidative response enzymes. We measured headspace NO above primary airway cells without and with a PCD-causing genotype. We measured nNO and exhaled breath condensate (EBC) H2O2 in vivo. Apical Derp1-f was cleared from HC better than from PCD cells. DUOX1 expression was lower in HC than in PCD cells at baseline and after 24-h Derp1-f exposure. HC cells had less 3-NT and NO3- than PCD cells. However, NO consumption by HC cells was less than that by PCD cells; NO loss was prevented by superoxide dismutase (SOD) and by apocynin. nNO was higher in HCs than in patients with PCD. EBC H2O2 was lower in HC than in patients with PCD. The PCD airway epithelium does not optimally clear antigens and is subject to oxidative and nitrosative stress. Oxidation associated with antigen stasis could represent a therapeutic target in PCD, one with convenient monitoring biomarkers.NEW & NOTEWORTHY The PCD airway epithelium does not optimally clear antigens, and antigen exposure can lead to NO oxidation and nitrosative stress. Oxidation caused by antigen stasis could represent a therapeutic target in PCD, and there are convenient monitoring biomarkers.

"You Can Do So Much Better Than What They Expect": An Arts-Based Engagement Ethnography on School Integration With Newcomer Youth.

Newcomer adolescents make up a large minority of Canada's population and their positive integration experiences with education systems across the country are critical for both their development and the country's long-term success. The current study examined newcomer adolescents' (n = 4, between 16 and 18 years old) integration experiences using an arts-based engagement ethnography to understand what influences their positive integration into the school system. Artifacts, interview, and focus group data were analyzed systematically using ethnographic research guidelines. Five structures were identified: (1) barriers to advancement at individual, school, and macro levels, (2) fluctuating relationship with cultural identity, (3) limited trust in systems, (4) resilience through independent learning, and (5) facilitating factors to positive integration experiences at the family and school level. In keeping with a relational developmental systems theory framework, each structure accounts for multiple inter- and intra-individual factors at multiple environmental levels. These findings outline considerations for systemic issues in academic institutions and offer suggestions for how institutions can better support newcomer adolescents.

Early childhood growth in Daasanach pastoralists of Northern Kenya: Distinct patterns of faltering in linear growth and weight gain.

OBJECTIVES: Investigations of early childhood growth among small-scale populations are essential for understanding human life history variation and enhancing the ability to serve such communities through global public health initiatives. This study characterizes early childhood growth trajectories and identifies differences in growth patterns relative to international references among Daasanach semi-nomadic pastoralist children living in a hot, arid region of northern Kenya. METHODS: A large sample of height and weight measures were collected from children (N = 1756; total observations = 4508; age = 0-5 years) between 2018 and 2020. Daasanach growth was compared to international reference standards and Daasanach-specific centile growth curves and pseudo-velocity models were generated using generalized additive models for location scale and size. RESULTS: Compared to World Health Organization (WHO) reference, relatively few Daasanach children were stunted (14.3%), while a large proportion were underweight (38.5%) and wasted (53.6%). Additionally, Daasanach children had a distinctive pattern of growth, marked by an increase in linear growth velocity after 24 months of age and relatively high linear growth velocity throughout the rest of early childhood. CONCLUSIONS: These results identify a unique pattern of early childhood growth faltering among children in a small-scale population and may reflect a thermoregulatory adaptation to their hot, arid environment. As linear growth and weight gain remain important indicators of health, the results of this study provide insight into growth velocity variations. This study has important implications for global public health efforts to identify and address sources of early growth faltering and undernutrition in small-scale populations.

A test for implicit bias in discretionary criminal justice decisions.

OBJECTIVE: Our goal was to develop a framework to test for implicit racial bias in discretionary decisions made by community supervision agents in conditions with increasing information ambiguity. HYPOTHESES: We reasoned that as in-person contact decreases, community supervision officers' specific knowledge of clients would be replaced by heuristics that lead to racially disproportionate outcomes in higher discretion events. Officers' implicit biases would lead to disproportionately higher technical violation rates among Black community corrections' clients when they have less personal contact, but we expected no analogous increase in nondiscretionary decisions. METHOD: Using data from Black and White clients entering probation and postrelease supervision in North Carolina from 2012 through 2016, we estimated the difference in racial disparities in discretionary versus nondiscretionary decisions across five levels of supervision. We evaluated the robustness of our main fixed-effects model using an alternative regression discontinuity design. RESULTS: Racial disparities in discretionary decisions grew as supervision intensity decreased, and the bias was larger for women than men. There was no similar pattern of increased disparity for nondiscretionary decisions. CONCLUSIONS: Criminal justice system actors have a great deal of discretion, particularly in how they deal with less serious criminal behavior. Although decentralized decisions are foundational to the function of the criminal justice system, they provide an opportunity for implicit bias to seep in. Shortcuts and mental heuristics are more influential when the decision-maker's mental resources are already strained-for instance, if someone is tired, distracted, or overworked. Therefore, limiting discretion and increasing oversight and accountability may reduce the impact of implicit bias on criminal justice system outcomes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Validation of a Farsi version of the Eating Pathology Symptoms Inventory (F-EPSI) among Iranian adolescents.

PURPOSE: Limited research has validated eating pathology assessments in Iranian adolescent boys and girls. In particular, the measures that have been validated do not capture both boys' and girls' eating behaviors in adolescence. The purpose of the current study was to validate a Farsi version of the Eating Pathology Symptoms Inventory (F-EPSI) for use in Iranian adolescents. METHODS: Participants (N = 913; 85.3% girls) were adolescents who completed a battery of questionnaires including the F-EPSI. In addition, F-EPSI data for Iranian adolescents were compared with those of previously published data of adult Iranian college students. RESULTS: Confirmatory Factor Analysis (CFA) indicated that the F-EPSI had an acceptable fit to the data and supported the eight-factor model. The scale was invariant by gender, weight status, eating disorder, and age groups. Boys reported higher scores than girls on the Excessive Exercise, Muscle Building, Body Dissatisfaction, and Binge Eating subscales. Adolescents with higher weight and eating disorder symptoms endorsed higher scores on the F-EPSI subscales. Older adolescents and adults reported higher scores than younger adolescents and adolescents, respectively. Adolescents had higher scores than adults on Restricting and Excessive Exercise subscales. The F-EPSI demonstrated good convergent validity through correlations with other eating pathology symptoms. The F-EPSI subscales were associated with depression and body mass index (zBMI) in expected directions that indicate criterion validity of the scale. CONCLUSIONS: Findings suggest that the F-EPSI is a reliable and valid measure in Iranian non-clinical adolescents. The F-EPSI will enable researchers to examine a broad array of eating pathology symptoms in adolescents for whom Farsi is their official language. LEVEL OF EVIDENCE: Level V; Cross-sectional descriptive study.

The validation of a Farsi version of the Clinical Impairment Assessment (F-CIA) among Iranian adolescent boys and girls.

PURPOSE: Although some studies have been conducted to examine general psychosocial impairment in Iran, there is no research to date on clinical impairment secondary to disordered eating in Iranian adolescents. The purpose of this study was to evaluate the Farsi version of the Clinical Impairment Assessment (F-CIA) among Iranian adolescents. METHODS: A total of 1112 adolescents (ageM [SD] = 15.55 [1.59], body mass index [zBMI] M [SD] = - 0.00 [1.0]; 54.6% girls) were recruited from four cities (Tehran [Capital], Tabriz [North-Western], Kurdistan [West], and Rasht [North]) in Iran. After translation and back-translation procedures, the F-CIA, Eating Disorder Examination Questionnaire (EDE-Q), and Beck Depression Inventory-Second Edition (BDI-II) were administered to adolescents. We used confirmatory factor analysis (CFA), measurement invariance, independent samples t tests, Pearson correlation, chi-square tests, and internal consistency to test validity and reliability. RESULTS: CFA indicated that F-CIA demonstrated good fit to the data and supported a three-factor model. The scale was invariant across gender and zBMI. The F-CIA had good internal consistency (αs = 0.76-0.93) and positive associations (rs = 0.13-0.62; p < 0.001) with zBMI, disordered eating symptoms, and binge/purge symptoms. We found no gender differences across mean scores on the F-CIA, but adolescents with higher zBMI reported higher scores on the F-CIA relative to those with lower zBMIs. Finally, adolescents scoring above CIA cutoffs reported higher zBMI, disordered eating outcomes, and depression. CONCLUSION: Findings suggested that the F-CIA is a reliable and valid measure of clinical eating disorder-related impairment in Iranian adolescents. LEVEL OF EVIDENCE: III; Evidence obtained from well-designed observational study, including case-control design for relevant aspects of the study.

Systematic evaluation of structure-property relationships and pharmacokinetics in 6-(hetero)aryl-substituted matched pair analogs of amiloride and 5-(N,N-hexamethylene)amiloride.

The K+-sparing diuretic amiloride elicits anticancer activities in multiple animal models. During our recent medicinal chemistry campaign aiming to identify amiloride analogs with improved properties for potential use in cancer, we discovered novel 6-(hetero)aryl-substituted amiloride and 5-(N,N-hexamethylene)amiloride (HMA) analogs with up to 100-fold higher potencies than the parent compounds against urokinase plasminogen activator (uPA), one of amiloride's putative anticancer targets, and no diuretic or antikaliuretic effects. Here, we report the systematic evaluation of structure-property relationships (lipophilicity, aqueous solubility and in vitro metabolic stability in human and mouse liver microsomes) in twelve matched pair analogs selected from our 6-substituted amiloride and HMA libraries. Mouse plasma stability, plasma protein binding, Caco-2 cell permeability, cardiac ion channel activity and pharmacokinetics in mice (PO and IV) and rats (IV) are described alongside amiloride and HMA comparators for a subset of the four most promising matched-pair analogs. The findings combined with earlier uPA activity/selectivity and other data ultimately drove selection of two analogs (AA1-39 and AA1-41) that showed efficacy in separate mouse cancer metastasis studies.

Quantifying Proximal Collecting Tubule Deficiency in Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Fetopathy.

INTRODUCTION: Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers (AAs) are used for several indications, with cessation recommended in pregnancy due to toxic effects. AA fetopathy phenotype is similar to renal tubular dysgenesis including reduced proximal convoluted tubules (PCTs). Our study aimed to quantify the reduction of PCTs in fetuses and infants with prenatal exposure to AAs. MATERIALS AND METHODS: We identified 5 fetal AA exposure cases that underwent autopsy at our institution between 2011 and 2018 and compared with 5 gestational age-matched controls. Immunohistochemistry with CD10 and epithelial membrane antigen (EMA) was utilized. RESULTS: CD10 and EMA identified a median PCT density of 19.0% ± 12.3% in AA fetopathy patients, significantly less than controls (52.8% ± 4.4%; p < 0.0001). One case with in utero cessation had a PCT density of 34.2% ± 0.2%. Among other AA fetopathy findings, 1 case demonstrated unilateral renal vein thrombosis and 4 had hypocalvaria. CONCLUSIONS: We have quantified the reduction in AA fetopathy PCT density, and demonstrated in utero cessation may recover PCT differentiation. Future studies may benefit from calculating PCT percentage as a potential biomarker to correlate with post-natal renal function and maternal factors including medication type, dosage, duration, and time from medication cessation.

Eating disorder symptoms among adolescent boys and girls in Iran.

OBJECTIVE: Few studies of eating disorder (ED) symptoms among young people in Iran have been conducted. This cross-sectional study examined ED symptoms, assessed by the Eating Disorder Examination Questionnaire (EDE-Q). METHOD: Adolescent boys (n = 498) and girls (n = 607) aged 12-19 years, recruited from schools in four different regions of Iran, completed a survey that included the EDE-Q. ED symptoms, namely, EDE-Q global scores and the occurrence of specific ED behaviors, were compared between boys and girls. RESULTS: Girls had higher global scores and were more likely to report regular extreme dietary restriction than boys (16.6 vs. 12.0%). The effect sizes for these differences were small. The regular occurrence of other behaviors (girls vs. boys-binge eating: 21.1 vs. 18.8%; self-induced vomiting: 3.3 vs. 5.4%; laxative misuse: 6.1 vs. 7.6%; excessive exercise: 5.3 vs. 4.4%) did not significantly differ by gender. Twelve percent of boys and 12.9% of girls met criteria for an operational definition of "probable ED case." CONCLUSION: ED symptoms appear to be relatively common among Iranian adolescent boys and girls. Programs designed to reduce the occurrence and adverse impact of these symptoms may therefore be increasingly important.

Disordered eating, self-esteem, and depression symptoms in Iranian adolescents and young adults: A network analysis.

OBJECTIVE: The network theory of psychopathology examines networks of interconnections across symptoms. Several network studies of disordered eating have identified central and bridge symptoms in Western samples, yet network models of disordered eating have not been tested in non-Western samples. The current study tested a network model of disordered eating in Iranian adolescents and college students, as well as models of co-occurring depression and self-esteem. METHOD: Participants were Iranian college students (n= 637) and adolescents (n = 1,111) who completed the Eating Disorder Examination-Questionnaire (EDE-Q), Rosenberg Self-Esteem Scale (RSES) and Beck Depression Inventory, Second Edition (BDI-II). We computed six Glasso networks and identified central and bridge symptoms. RESULTS: Central disordered eating nodes in most models were a desire to lose weight and discomfort when seeing one's own body. Central self-esteem and depression nodes were feeling useless and self-dislike, respectively. Feeling like a failure was the most common bridge symptom between disordered eating and depression symptoms. With exception of a few differences in some edges, networks did not significantly differ in structure. DISCUSSION: Desire to lose weight was the most central node in the networks, which is consistent with sociocultural theories of disordered eating development, as well as prior network models from Western-culture samples. Feeling like a failure was the most central bridge symptom between depression and disordered eating, suggesting that very low self-esteem may be a shared correlate or risk factor for disordered eating and depression in Iranian adolescents and young adults.

Towards a sociocultural model of weight stigma.

PURPOSE: Weight stigma is pervasive and is associated with numerous physical and psychological health consequences, including decreased body satisfaction. Understanding of contributing factors to weight stigma remains limited, although researchers have consistently documented the connection between weight controllability beliefs and weight stigma. Sociocultural factors, including thin-ideal internalization and related social-cognitive correlates, are in the nascent stages of exploration to further our understanding of weight stigma. METHODS: In this study, we tested an emerging sociocultural model of weight stigma, examining the influence of thin-ideal internalization and appearance-related comparisons on weight stigma, statistically controlling for weight controllability beliefs and accounting for thin-ideal environmental influences. Participants were 137 MTurk workers living in the United States. RESULTS: We found that increased thin-ideal information was associated with thin-ideal internalization, which in turn was related to both upward and downward appearance-related comparison tendencies. These comparisons were then significantly related to weight stigma, controlling for weight controllability beliefs. There were significant indirect effects of both upward and downward appearance-related comparison tendencies on the relation between thin-ideal internalization and weight stigma. CONCLUSION: These results extend limited prior research examining the association between the thin-ideal and appearance-related comparisons with weight stigma, and contribute to a more nuanced understanding of this complex phenomenon. LEVEL OF EVIDENCE: Level V, cross-sectional study.

An in vitro toolbox to accelerate anti-malarial drug discovery and development.

BACKGROUND: Modelling and simulation are being increasingly utilized to support the discovery and development of new anti-malarial drugs. These approaches require reliable in vitro data for physicochemical properties, permeability, binding, intrinsic clearance and cytochrome P450 inhibition. This work was conducted to generate an in vitro data toolbox using standardized methods for a set of 45 anti-malarial drugs and to assess changes in physicochemical properties in relation to changing target product and candidate profiles. METHODS: Ionization constants were determined by potentiometric titration and partition coefficients were measured using a shake-flask method. Solubility was assessed in biorelevant media and permeability coefficients and efflux ratios were determined using Caco-2 cell monolayers. Binding to plasma and media proteins was measured using either ultracentrifugation or rapid equilibrium dialysis. Metabolic stability and cytochrome P450 inhibition were assessed using human liver microsomes. Sample analysis was conducted by LC-MS/MS. RESULTS: Both solubility and fraction unbound decreased, and permeability and unbound intrinsic clearance increased, with increasing Log D7.4. In general, development compounds were somewhat more lipophilic than legacy drugs. For many compounds, permeability and protein binding were challenging to assess and both required the use of experimental conditions that minimized the impact of non-specific binding. Intrinsic clearance in human liver microsomes was varied across the data set and several compounds exhibited no measurable substrate loss under the conditions used. Inhibition of cytochrome P450 enzymes was minimal for most compounds. CONCLUSIONS: This is the first data set to describe in vitro properties for 45 legacy and development anti-malarial drugs. The studies identified several practical methodological issues common to many of the more lipophilic compounds and highlighted areas which require more work to customize experimental conditions for compounds being designed to meet the new target product profiles. The dataset will be a valuable tool for malaria researchers aiming to develop PBPK models for the prediction of human PK properties and/or drug-drug interactions. Furthermore, generation of this comprehensive data set within a single laboratory allows direct comparison of properties across a large dataset and evaluation of changing property trends that have occurred over time with changing target product and candidate profiles.

Loss of BRG1 (SMARCA4) Immunoexpression in a Pediatric Non-Central Nervous System Tumor Cohort.

Malignant rhabdoid tumors and atypical teratoid/rhabdoid tumors of the central nervous system are primitive malignancies associated with a poor prognosis. These tumors have previously been characterized by inactivation of the switch/sucrose nonfermenting (SWI/SNF) chromatin remodeling complex protein integrase interactor 1 (INI1), encoded by the SMARCB1 gene. In the last decade, sporadic publications have shown that a different SWI/SNF protein, brahma-related gene 1 (BRG1), encoded by the SMARCA4 gene, is associated with a similar rhabdoid phenotype and possible germline mutation termed rhabdoid tumor predisposition syndrome type 2. We sought to determine the presence of BRG1 expression in pediatric embryonal tumors. Using a local tissue microarray consisting of 28 tumors diagnosed as having an undifferentiated, polyphenotypic, or rhabdoid morphology, expression of BRG1 by immunohistochemistry was performed. Four cases showed loss of INI1, while 3 of the remaining 24 cases demonstrated loss of BRG1. Two cases were diagnosed as soft tissue sarcomas, and 1 case was diagnosed as a small cell carcinoma of the ovary, hypercalcemic type. Survival ranged from less than 6 months after diagnosis to more than 5 years at the time of last follow-up. In conclusion, we demonstrate that BRG1 immunohistochemistry is a useful second-line immunostain for the workup of undifferentiated, polyphenotypic or rhabdoid pediatric tumors that demonstrate retained expression of INI1.

Improving Patient Experience and Treatment Adherence in the Adult, Outpatient Hemodialysis Population.

BACKGROUND: The commonly employed medication reconciliation process leaves room for mismanagement of medications in the complex end-stage renal disease patient population. PURPOSE: The purpose of this quality improvement project was to implement and evaluate a multidisciplinary education and feedback intervention designed to improve self-management for adults with end-stage renal disease. METHODS: A pre-post, same subject repeated measures design was used to evaluate the intervention. Laboratory values, vital signs, interdialytic weight gains, dialysis attendance, and questionnaires were used to assess regimen adherence. RESULTS: We observed improvements in patient outcomes including laboratory values, vital signs, and interdialytic weight gains. Significant improvements in process outcomes were also seen, including accuracy of medication lists, dialysis attendance, and use of remote pharmacy services. CONCLUSIONS: A comprehensive medication review, with concurrent pharmacist access, represents a time-effective approach to improved self-management and end-stage renal disease outcomes.

Disordered Society: Women in Eating Disorder Recovery Advise Policymakers on Change.

This qualitative study draws on a photo-elicitation method ("PhotoVoice") and semi-structured interviews to examine the key areas stakeholders (30 young women between the ages of 18 and 35 in eating disorder recovery) identify as meaningful venues of policy-based change. Photography and the accompanying narratives capturing personally-meaningful social, cultural, and systemic influences on recovery were shared with the research team. Photographs and interviews were examined for policy implications using thematic analysis, and six areas of improvement emerged: media, healthcare practice and access, health insurance reform, education, objectification of the female body, and mental health stigma. Implications for reform are discussed.

Using Human Plasma as an Assay Medium in Caco-2 Studies Improves Mass Balance for Lipophilic Compounds.

PURPOSE: To examine the utility of human plasma as an assay medium in Caco-2 permeability studies to overcome poor mass balance and inadequate sink conditions frequently encountered with lipophilic compounds. METHODS: Caco-2 permeability was assessed for reference compounds with known transport mechanisms using either pH 7.4 buffer or human plasma as the assay medium in both the apical and basolateral chambers. When using plasma, Papp values were corrected for the unbound fraction in the donor chamber. The utility of the approach was assessed by measuring the permeability of selected antimalarial compounds using the two assay media. RESULTS: Caco-2 cell monolayer integrity and P-gp transporter function were unaffected by the presence of human plasma in the donor and acceptor chambers. For many of the reference compounds having good mass balance with buffer as the medium, higher Papp values were observed with plasma, likely due to improved acceptor sink conditions. The lipophilic antimalarial compounds exhibited low mass balance with buffer, however the use of plasma markedly improved mass balance allowing the determination of more reliable Papp values. CONCLUSIONS: The results support the utility of human plasma as an alternate Caco-2 assay medium to improve mass balance and permeability measurements for lipophilic compounds.

Social comparisons in eating disorder recovery: Using PhotoVoice to capture the sociocultural influences on women's recovery.

OBJECTIVE: This qualitative study draws on a photo-elicitation method ("PhotoVoice") and semistructured interviews to examine the role of social comparison during the eating disorder (ED) recovery process. METHOD: Thirty U.S. women in self-defined recovery, ages 18-35, used photography to capture personally meaningful social and cultural influences on their recovery, including factors supporting, and hindering their recovery process. Participants then shared these photographs with the research team, and described them in detail. RESULTS: Photographs and interviews were examined for social comparisons using thematic analysis, and two broad categories emerged: recovery-promoting and recovery-hindering comparisons. Across the 30 interviews, participants reported 143 recovery hindering comparisons and 100 recovery promoting comparisons. The vast majority of comparisons involved friends and media personalities, and took place in vivo or on social media platforms. The presence of "upward" and "downward" food and body comparisons that both support and hinder recovery suggests that social comparisons during the recovery process are more nuanced than previously known. DISCUSSION: The classically ascribed uses of comparison in social comparison theory do not appear to hold for women in ED recovery. Comparisons should be encouraged in treatment and interventions if and only if the comparisons are meant to support the recovery process.

Body Dissatisfaction in Early Adolescence: The Coactive Roles of Cognitive and Sociocultural Factors.

The sociocultural influences of the media, friends, and family on body dissatisfaction in young girls are well documented, yet further increasing our comprehension of the coaction of cognitive processes with sociocultural factors is crucial to understanding the dynamic emergence of body dissatisfaction in early adolescence. The current study examined the roles of appearance related messages and expectations from friends and family and selective attention biases in the development of body dissatisfaction. An ethnically and racially diverse sample of girls (72 % Hispanic White, 17.8 % African-American, 8.5 % non-Hispanic White, and 1.7 % Asian-American) between the ages of 9 and 13 (N = 118) completed multiple measures of attention, sociocultural attitudes toward weight and shape, and body dissatisfaction. The data from these measures were examined using path analysis. The final model fit well, and demonstrated the coactive effect of selective attention and sociocultural factors on body dissatisfaction. These findings will be instrumental in designing future body dissatisfaction intervention and prevention programs that incorporate cognitive factors, augmenting the existing sociocultural and psycho-educational frameworks.

Self-esteem, diet self-efficacy, body mass index, and eating disorders: modeling effects in an ethnically diverse sample.

PURPOSE: Disordered eating patterns, particularly binge eating, are prevalent in Hispanic samples, yet the biopsychosocial risk factors remain understudied in minority populations. The relationship between diet self-efficacy and bulimic symptoms has been established in non-Hispanic white samples but not yet in Hispanics. This study sought to identify the direct role of diet self-efficacy on eating disorder risk and symptomology in a multicultural Hispanic sample, and to investigate the potential indirect relations among diet self-efficacy, self-esteem, body mass index (BMI), and eating disorder risk and symptomology in Hispanics and non-Hispanic whites. METHODS: The present study surveyed 1339 college students from diverse ethnic backgrounds. Participants completed four standardized scales to assess acculturation, diet self-efficacy, global self-esteem, and eating disorder symptomology and risk. Self-reported height and weight were used for BMI calculations, and the data were analyzed in a robust maximum-likelihood structural equation modeling (SEM) framework. RESULTS: The findings highlighted diet self-efficacy as a predictor of eating disorder risk and symptomology. Diet self-efficacy partially explained the covariation between self-esteem and eating disorder risk and symptomology, and between BMI and eating disorder risk and symptomology for the entire sample. CONCLUSION: Diet self-efficacy emerged as an important construct to consider in developing eating disorder prevention and treatment models.

ELQ-300 prodrugs for enhanced delivery and single-dose cure of malaria.

ELQ-300 is a preclinical candidate that targets the liver and blood stages of Plasmodium falciparum, as well as the forms that are crucial to transmission of disease: gametocytes, zygotes, and ookinetes. A significant obstacle to the clinical development of ELQ-300 is related to its physicochemical properties. Its relatively poor aqueous solubility and high crystallinity limit absorption to the degree that only low blood concentrations can be achieved following oral dosing. While these low blood concentrations are sufficient for therapy, the levels are too low to establish an acceptable safety margin required by regulatory agencies for clinical development. One way to address the challenging physicochemical properties of ELQ-300 is through the development of prodrugs. Here, we profile ELQ-337, a bioreversible O-linked carbonate ester prodrug of the parent molecule. At the molar equivalent dose of 3 mg/kg of body weight, the delivery of ELQ-300 from ELQ-337 is enhanced by 3- to 4-fold, reaching a maximum concentration of drug in serum (C max) of 5.9 µM by 6 h after oral administration, and unlike ELQ-300 at any dose, ELQ-337 provides single-dose cures of patent malaria infections in mice at low-single-digit milligram per kilogram doses. Our findings show that the prodrug strategy represents a viable approach to overcome the physicochemical limitations of ELQ-300 to deliver the active drug to the bloodstream at concentrations sufficient for safety and toxicology studies, as well as achieving single-dose cures.