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Dimethyl sulfoxide (DMSO) has wide biomedical applications such as cryoprotectant and hydrophobic drug carrier. Here, we report for the first time that DMSO can generate a distinctive chemical exchange saturation transfer (CEST) signal at around -2 ppm. Structural analogs of DMSO, including aprotic and protic solvents, also demonstrated CEST signals from -1.4 to -3.8 ppm. When CEST detectable barbituric acid (BA) was dissolved in DMSO solution and was co-loaded to liposome, two obvious peaks at 5 and -2 ppm were observed, indicating that DMSO and related solvent system can be monitored in a label-free manner via CEST, which can be further applied to imaging drug nanocarriers. With reference to previous studies, there could be molecular interactions or magnetization transfer pathways, such as the relayed nuclear Overhauser enhancement (rNOE), that lead to this detectable CEST contrast at negative offset frequencies of the Z-spectrum. Our findings suggest that small molecules of organic solvents could be involved in magnetization transfer processes with water and readily detected by CEST magnetic resonance imaging (MRI), providing a new avenue for detecting solvent-water and solvent-drug interactions., (© 2024 The Author(s). NMR in Biomedicine published by John Wiley & Sons Ltd.)

Image guided nose-to-brain drug delivery provides a non-invasive way to monitor drug delivered to the brain, and the intranasal administration could increase effective dose via bypassing Blood Brain Barrier (BBB). Here, we investigated the imaging of liposome-based drug delivery to the brain via intranasal administration, in which the liposome could penetrate mucus and could be detected by chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) at 3T field strength. Liposomes were loaded with a computed tomography (CT) contrast agent, iohexol (Ioh-Lipo), which has specific amide protons exchanging at 4.3 ppm of Z-spectrum (or CEST spectrum). Ioh-Lipo generated CEST contrasts of 35.4% at 4.3 ppm, 1.8% at -3.4 ppm and 20.6% at 1.2 ppm in vitro. After intranasal administration, these specific CEST contrasts were observed in both olfactory bulb (OB) and frontal lobe (FL) in the case of 10% polyethylene glycol (PEG) Ioh-Lipo. We observed obvious increases in CEST contrast in OB half an hour after the injection of 10% PEG Ioh-Lipo, with a percentage increase of 62.0% at 4.3 ppm, 10.9% at -3.4 ppm and 25.7% at 1.2 ppm. Interestingly, the CEST map at 4.3 ppm was distinctive from that at -3.4 pm and 1.2 ppm. The highest contrast of 4.3 ppm was at the external plexiform layer (EPL) and the region between left and right OB (LROB), while the CEST contrast at -3.4 ppm had no significant difference among all investigated regions with slightly higher signal in olfactory limbus (OL, between OB and FL) and FL, as validated with histology. While no substantial increase of CEST contrast at 4.3 ppm, -3.4 ppm or 1.2 ppm was observed in OB and FL when 1% PEG Ioh-Lipo was administered. We demonstrated for the first time the feasibility of non-invasively detecting the nose-to-brain delivery of liposomes using CEST MRI. This multiple-contrast approach is necessary to image the specific distribution of iohexol and liposome simultaneously and independently, especially when designing drug carriers for nose-to-brain drug delivery., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Imaging pHe of the tumor microenvironment has paramount importance for characterizing aggressive, invasive tumors, as well as therapeutic responses. Here, a robust approach to image pH changes in the tumor microenvironment longitudinally and during sodium bicarbonate treatment was reported. The pH-sensing microbeads were designed and prepared based on materials approved for clinical use, i.e., alginate microbead-containing computed tomography (CT) contrast-agent (iopamidol)-loaded liposomes (Iop-lipobeads). This Iop-lipobead prepared using a customized microfluidic device generated a CEST contrast of 10.6% at 4.2 ppm at pH 7.0, which was stable for 20 days in vitro. The CEST contrast decreased by 11.8% when the pH decreased from 7.0 to 6.5 in vitro. Optimized Iop-lipobeads next to tumors showed a significant increase of 19.7 ± 6.1% ( p < 0.01) in CEST contrast at 4.2 ppm during the first 3 days of treatment and decreased to 15.2 ± 4.8% when treatment stopped. Notably, percentage changes in Iop-lipobeads were higher than that of amide CEST (11.7% and 9.1%) in tumors during and after treatment. These findings demonstrated that the Iop-lipobead could provide an independent and sensitive assessment of the pHe changes for a noninvasive and longitudinal monitoring of the treatment effects using multiple CEST contrast.

Background: Few intervention studies have integrated cultural tailoring, parenting, behavioral, and motivational strategies to address African American adolescent weight loss., Purpose: The Families Improving Together (FIT) for Weight Loss trial was a randomized group cohort study testing the efficacy of a cultural tailoring, positive parenting, and motivational intervention for weight loss in overweight African American adolescents (N = 241 adolescent/caregiver dyads)., Methods: The trial tested an 8-week face-to-face group motivational plus family weight loss program (M + FWL) compared with a comprehensive health education control program. Participants were then rerandomized to an 8-week tailored or control online program to test the added effects of the online intervention on reducing body mass index and improving physical activity (moderate-to-vigorous physical activity [MVPA], light physical activity [LPA]), and diet., Results: There were no significant intervention effects for body mass index or diet. There was a significant effect of the group M + FWL intervention on parent LPA at 16 weeks (B = 33.017, SE = 13.115, p = .012). Parents in the group M + FWL intervention showed an increase in LPA, whereas parents in the comprehensive health education group showed a decrease in LPA. Secondary analyses using complier average causal effects showed a significant intervention effect at 16 weeks for parents on MVPA and a similar trend for adolescents., Conclusions: While the intervention showed some impact on physical activity, additional strategies are needed to impact weight loss among overweight African American adolescents., (© Society of Behavioral Medicine 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The current study is a randomized controlled trial to test a novel 10-week climate-based intervention within pre-existing afterschool programs, designed to increase moderate-to-vigorous physical activity (MVPA) in underserved (low-income, minority status) middle school youth by addressing youth social developmental needs. Participants (n = 167; 56% female; 62% Black; 50% overweight/obese) enrolled in 6 middle schools were randomized to either the Connect through PLAY intervention or a wait-list control. Process evaluation measures (i.e., observations of external evaluators; staff surveys) indicated that essential elements were implemented with fidelity, and staff endorsed implementation ease/feasibility and acceptability. Regression analysis demonstrated that participation in the intervention (vs. control) was associated with an increase of 8.17 min of daily accelerometry-measured MVPA (56 min of additional weekly MVPA) at post-intervention controlling for baseline MVPA, school, gender, and weight status. The results provide support for social-motivational climate-based interventions for increasing MVPA in underserved youth that can inform future school-based health initiatives.Trial Registration: NCT03850821: https://clinicaltrials.gov/ct2/show/study/NCT03850821?term=NCT03850821&rank=1.

Short circulation lifetime, poor blood-brain barrier (BBB) permeability and low targeting specificity limit nanovehicles from crossing the vascular barrier and reaching the tumor site. Consequently, the precise diagnosis of malignant brain tumors remains a great challenge. This study demonstrates the imaging of photostable biopolymer-coated nanodiamonds (NDs) with tumor targeting properties inside the brain. NDs are labeled with PEGylated denatured bovine serum albumin (BSA) and tumor vasculature targeting tripeptides RGD. The modified NDs show high colloidal stability in different buffer systems. Moreover, it is found that discrete dcBSA-PEG-NDs cross the in vitro BBB model more effectively than aggregated NDs. Importantly, compared with the non-targeting NDs, RGD-dcBSA-PEG-NDs can selectively target the tumor site in U-87 MG bearing mice after systemic injection. Overall, this discrete ND system enables efficacious brain tumor visualization with minimal toxicity to other major organs, and is worthy of further investigation into the applications as a unique platform for noninvasive theragnostics and/or thermometry at different stages of human diseases in the brain.

Climate-based weight loss interventions, or those that foster a nurturing family environment, address important ecological influences typically ignored by the traditional biomedical treatments. Promoting a climate characterized by positive communication, autonomy support, and parental warmth supports adolescents in making healthy behavioral changes. In addition, encouraging these skills within the family may have additional benefits of improved family functioning and other mental and physical health outcomes. Although several programs have identified essential elements and established the evidence base for the efficacy of these interventions, few have offered resources for the translation of these constructs from theoretical concepts to tangible practice. This paper provides strategies and resources utilized in the Families Improving Together (FIT) for weight loss randomized controlled trial to create a warm, supportive climate characterized by positive communication within the parent-child relationship. Detailed descriptions of how Project FIT emphasized these constructs through facilitator training, intervention curriculum, and process evaluation are provided as a resource for clinical and community interventions. Researchers are encouraged to provide resources to promote translation of evidence-based interventions for programs aiming to utilize a positive climate-based family approach for lifestyle modification., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Behavioral Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Interventions that incorporate behavioral skills training and parental involvement have been effective for promoting weight loss among middle and upper class youth; however, few studies have produced similar weight loss effects in underserved ethnic minority youth., Purpose: This study examined whether online program exposure (in both an online tailored intervention and an online health education comparison program) predicted greater retention among African American youth and their parents in the Families Improving Together (FIT) for Weight Loss trial., Methods: Parent-adolescent dyads (N = 125) were randomized to either an online tailored intervention program (n = 63) or an online health education comparison program (n = 62). Paradata including login data were used to determine the number of sessions viewed (0-8) and the number of minutes spent online per session. Study retention, defined as collection of adolescent anthropometric measures at 6 months postintervention, was the outcome., Results: Logistic regression analyses showed a significant effect for login rate on retention (OR = 1.21, 95% CI [1.04, 1.39]). Total number of sessions viewed, child age, child sex, parent age, and parent sex accounted for 11% of the variance in retention at 6 months post- intervention. Participants who were retained spent a significantly greater number of minutes during each session (M = 12.99, SD = 11.63) than participants who were not retained (M = 7.77, SD = 11.19), t(123) = 2.24, p = .027, d = 0.45., Conclusions: The use of paradata from online interventions is a novel and feasible approach for examining exposure in web-based interventions and program retention in underserved ethnic minority families., Trial Registration: ClinicalTrials.gov NCT01796067. Registered January 23, 2013., (© Society of Behavioral Medicine 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)