Freezing-mediated formation of supraproteins using depletion forces.

Hypothesis Long-acting formulations such as microparticles, injectable depots and implantable devices can realize spatiotemporally controlled delivery of protein drugs to extend their therapeutic in vivo half-lives. To efficiently encapsulate the protein drugs into such drug delivery systems, (sub)micron-sized protein particles are needed. The formation of micronized supraproteins can be induced through the synergistic combination of attractive depletion forces and freezing. The size of the supraproteins can be fine-tuned from submicron to several microns by adjusting the ice crystallization rate through the freeze-quench depth, which is set by the target temperature. Methods Supraprotein micron structures were prepared from protein solutions under various conditions in the presence and absence of nonadsorbing polyethylene glycol. Scanning electron microscopy and dynamic light scattering were employed to determine the sizes of the supraproteins and real-time total internal reflection fluorescent microscopy was used to follow the supraprotein formation during freezing. The protein secondary structure was measured before and after micronization by circular dichroism. A phase diagram of a protein-polyethylene glycol mixture was theoretically predicted to investigate whether the depletion interaction can elucidate the phase behavior. Findings Micronized protein supraparticles could be prepared in a controlled manner by rapid freeze-drying of aqueous mixtures of bovine serum albumin, horseradish peroxidase and lysozyme mixed with polyethylene glycol. Upon freezing, the temperature quench initiates a phase separation process which is reminiscent of spinodal decomposition. This demixing is subsequently arrested during droplet phase separation to form protein-rich microstructures. The final size of the generated protein microparticles is determined by a competition between phase separation and cooling rate, which can be controlled by target temperature. The experimental phase diagram of the aqueous protein-polyethylene glycol dispersion aligns with predictions from depletion theory for charged colloids and nonadsorbing polymers.

Accessible weight loss program for adults who are legally blind: A pilot study.

BACKGROUND: Compared to those without vision impairments, adults with low vision have higher rates of obesity and face more barriers to participation in traditional weight loss programs. OBJECTIVE: This pilot study examined the usability and helpfulness of an adaptive, evidence-based weight loss program for adults who are legally blind. METHODS: The study was a remotely delivered, single-arm weight loss trial for adults who were legally blind with a body mass index (BMI) ≥ 25. At weeks 4 and 8, participants reported usability and helpfulness of program components using a five-point scale (0-4) with higher numbers indicating greater usability and helpfulness. Weight data were collected at baseline, week 4, and week 8 using a scale with cellular technology. The adaptive 8-week weight loss program included evidence-based lifestyle recommendations for diet, physical activity, and self-weighing. The program provided support through text messages, emails, and video-based problem-solving sessions. RESULTS: Participants (N = 28) were aged 53.4 ± 10.2 years, 89.3% female, 35.7% Black, and 57.1% non-Hispanic White with an average BMI of 35.4 ± 8.8 kg/m2. Most program components had a median score of 4 for usability and helpfulness except educational materials (helpfulness, median 3). Compared to baseline weight, participants had a weight loss of 2.2 ± 2.1% (p < .001) at week 4 and 3.6 ± 3.0% (p < .001) at week 8. CONCLUSIONS: This study has provided evidence that an all-remote weight loss program can be a useable, helpful, and effective approach for adults who are legally blind. More work is needed to develop scalable, sustainable, and fully accessible evidence-based weight loss programs. TRIAL REGISTRATION: Clinicaltrials. gov identifier: NCT05419063.

Long-term retention in an employer-based, commercial weight-loss programme.

The aim of this study is to examine factors associated with long-term retention in a commercial weight-loss programme. We conducted a retrospective analysis of an employer-based, commercial programme from 2013 to 2016. Our dependent variable was 'long-term retention', defined as continuously enrolled participants who actively engaged through coach calls at 6 and 12 months. Independent variables included baseline demographics, programme engagement and weight change. We conducted multivariate logistic regression analyses assessing for differences in long-term retention by several factors, adjusted for employer clustering. Overall, 68.3% were retained at 6% and 45.9% at 12 months. Greater number of coach calls and website logins during the first 3 months significantly increased the odds of long-term retention, while having chronic conditions significantly decreased the odds. Weight-loss success (≥5% loss at 6 months) was significantly associated with increased odds of retention (12-month: odds ratio [OR] 2.80, P < 0.001), while early weight-loss failure (≥0% weight change at 1 month) significantly decreased odds of retention (12-month: OR 0.66, P = 0.008). In an employer-based, commercial weight loss programme, greater early programme engagement was associated with long-term retention. Given these programmes' popularity and potential reach, our results could be used to develop and test strategies designed to improve retention in commercial weight-loss programmes.

Factors associated with early dropout in an employer-based commercial weight-loss program.

OBJECTIVE: Minimizing program dropout is essential for weight-loss success, but factors that influence dropout among commercial programs are unclear. This study's objective was to determine factors associated with early dropout in a commercial weight-loss program. METHODS: A retrospective analysis of a remotely delivered, employer-based commercial program from 2013 to 2016 was conducted. The dependent variable was 'early dropout', defined as enrollees who disengaged from telephone coaching by month 2's end. Independent variables included demographics, program website engagement and early weight change. Multivariate logistic regression analyses were used to assess for differences in early dropout by several factors, adjusted for employer clustering. RESULTS: Of the 5,274 participants, 26.8% dropped out early. Having ≥1 chronic condition (odds ratio [OR] 1.41, p < 0.001) and 'weight-loss failure' defined as ≥0% weight change at month 1's end (OR 1.86, p < 0.001) had significantly increased odds of early dropout. Increasing age by 10-year intervals (OR 0.90, p = 0.002) and 'meeting the website login goal' defined as ≥90 logins in 3 months (OR 0.13, p < 0.001) significantly decreased the odds of early dropout. CONCLUSIONS: Presence of comorbidities, less online engagement and weight-loss failure were associated with early dropout in a commercial program. Strategies to prevent dropout among high-risk participants, such as increased support or program tailoring, should be developed and tested.

Design of block-copolymer-based micelles for active and passive targeting.

A self-consistent field study is presented on the design of active and passive targeting block-copolymeric micelles. These micelles form in water by self-assembly of triblock copolymers with a hydrophilic middle block and two hydrophobic outer blocks. A minority amount of diblock copolymers with the same chemistry is taken to coassemble into these micelles. At the end of the hydrophilic block of the diblock copolymers, a targeting moiety (TM) is present. Assuming that the rotation of the micelle towards the target is sufficiently fast, we can elaborate a single gradient cell model, wherein the micelle is in the center and the receptor (R) substrate exists on the outer plane of the spherical coordinate system. The distribution function of the targeting moiety corresponds to a Landau free energy with local minima and corresponding maxima. The lowest minimum, which is the ground state, shifts from within the micelle to the adsorbing state upon bringing the substrate closer to the micelle, implying a jumplike translocation of the targeting moiety. Equally deep minima represent the binodal of the phase transition, which is, due to the finite chain length, first-order like. The maximum in-between the two relevant minima implies that there is an activation barrier for the targeting moiety to reach the receptor surface. We localize the parameter space wherein the targeting moiety is (when the micelle is far from the target) preferably hidden in the stealthy hydrophilic corona of the micelle, which is desirable to avoid undesired immune responses, and still can jump out of the corona to reach the target quick enough, that is, when the barrier height is sufficiently low. The latter requirement may be identified by a spinodal condition. We found that such hidden TMs can still establish a TM-R contact at distances up to twice the corona size. The translocation transition will work best when the affinity of the TM for the core is avoided and when hydrophilic TMs are selected.

Formulation and antifungal performance of natamycin-loaded liposomal suspensions: the benefits of sterol-enrichment.

The aim of this study is to develop and evaluate food-grade liposomal delivery systems for the antifungal compound natamycin. Liposomes made of various soybean lecithins are prepared by solvent injection, leading to small unilamellar vesicles (<130 nm) with controlled polydispersity, able to encapsulate natamycin without significant modification of their size characteristics. Presence of charged phospholipids and reduced content of phosphatidylcholine in the lecithin mixture are found to be beneficial for natamycin encapsulation, indicating electrostatic interactions of the preservative with the polar head of the phospholipids. The chemical instability of natamycin upon storage in these formulations is however significant and proves that uncontrolled leakage out of the liposomes occurs. Efficient prevention of natamycin degradation is obtained by incorporation of sterols (cholesterol, ergosterol) in the lipid mixture and is linked to higher entrapment levels and reduced permeability of the phospholipid membrane provided by the ordering effect of sterols. Comparable action of ergosterol is observed at concentrations 2.5-fold lower than cholesterol and attributed to a preferential interaction of natamycin-ergosterol as well as a higher control of membrane permeability. Fine-tuning of sterol concentration allows preparation of liposomal suspensions presenting modulated in vitro release kinetics rates and enhanced antifungal activity against the model yeast Saccharomyces cerevisiae.

Psychosocial predictors of weight loss by race and sex.

This paper examined the psychosocial predictors of weight loss among race and sex subgroups. Analyses included overweight and obese participants from the PREMIER study, a previously published randomized trial that examined the effects of two multi-component lifestyle interventions on blood pressure among pre-hypertensive and stage 1 hypertensive adults. Both intervention conditions received behavioural recommendations for weight loss and group sessions. Weight and psychosocial measures of self-efficacy and social support for diet and exercise were assessed at baseline and at 6 months. There were 157 African-American (AA) women, 46 AA men, 203 non-AA women and 182 non-AA men with an average age of 50 years and average body mass index of 34 at baseline. Multiple predictor regression models were performed individually by race and sex subgroup. Among AA women, increases in diet self-efficacy were associated with weight loss. Among AA men, increases in diet-related social support and self-efficacy, along with increases in family support to exercise, were associated with weight loss (all Ps <0.05). Among non-AA women, increases in friends' support to exercise and exercise-related self-efficacy were associated with weight loss, and among non-AA men only increases in diet self-efficacy were associated with weight loss (all Ps <0.05). These results emphasize the need for targeted interventions based on race and sex to optimize the impact of lifestyle-based weight loss programmes.

Perceived helpfulness of the individual components of a behavioural weight loss program: results from the Hopkins POWER Trial.

BACKGROUND: Behavioural weight loss programs are effective first-line treatments for obesity and are recommended by the US Preventive Services Task Force. Gaining an understanding of intervention components that are found helpful by different demographic groups can improve tailoring of weight loss programs. This paper examined the perceived helpfulness of different weight loss program components. METHODS: Participants (n = 236) from the active intervention conditions of the Practice-based Opportunities for Weight Reduction (POWER) Hopkins Trial rated the helpfulness of 15 different components of a multicomponent behavioural weight loss program at 24-month follow-up. These ratings were examined in relation to demographic variables, treatment arm and weight loss success. RESULTS: The components most frequently identified as helpful were individual telephone sessions (88%), tracking weight online (81%) and coach review of tracking (81%). The component least frequently rated as helpful was the primary care providers' general involvement (50%). Groups such as older adults, Blacks and those with lower education levels more frequently reported intervention components as helpful compared with their counterparts. DISCUSSION: Weight loss coaching delivered telephonically with web support was well received. Findings support the use of remote behavioural interventions for a wide variety of individuals.

Controlled block copolymer micelle formation for encapsulation of hydrophobic ingredients.

We report on the formation of polymeric micelles in water using triblock copolymers with a polyethylene glycol middle block and various hydrophobic outer blocks prepared with the precipitation method. We form micelles in a reproducible manner with a narrow size distribution. This suggests that during the formation of the micelles the system had time to form micelles under close-to-thermodynamic control. This may explain why it is possible to use an equilibrium self-consistent field theory to predict the hydrodynamic size and the loading capacity of the micelles in accordance with experimental finding. Yet, the micelles are structurally quenched as concluded from the observation of size stability in time. We demonstrate that our approach enables to prepare rather hydrophobic block copolymer micelles with tunable size and loading.

Behavioral mediators of treatment effects in the weight loss maintenance trial.

BACKGROUND: The Weight Loss Maintenance Trial tested strategies for maintenance of weight loss. Personal contact was superior to interactive technology and self-directed conditions. PURPOSE: We aimed to identify behavioral mediators of the superior effect of personal contact vs. interactive technology and of personal contact vs. self-directed arms. METHODS: Overweight/obese adults at risk for cardiovascular disease (n = 1,032) who lost at least 4 kg were randomized to personal contact, interactive technology, or self-directed. After 30 months, 880 participants had data on weight and behavioral strategies. RESULTS: Reported increase of intake of fruits and vegetables and physical activity and more frequent self-weighing met criteria as mediators of the better outcome of personal contact vs. interactive technology. Increased intake of fruits and vegetables, more frequent self-weighing, and decreased dessert consumption were mediators of the difference between personal contact vs. self-directed. CONCLUSION: Inducing changes in the identified behaviors might yield better outcomes in future weight loss maintenance trials.

Patient-reported outcomes in the practice-based opportunities for weight reduction (POWER) trial.

PURPOSE: To evaluate effects of two behavioral weight-loss interventions (in-person, remote) on health-related quality of life (HRQOL) compared to a control intervention. METHODS: Four hundred and fifty-one obese US adults with at least one cardiovascular risk factor completed five measures of HRQOL and depression: MOS SF-12 physical component summary (PCS) and mental component summary; EuroQoL-5 dimensions single index and visual analog scale; PHQ-8 depression symptoms; and PSQI sleep quality scores at baseline and 6 and 24 months after randomization. Change in each outcome was analyzed using outcome-specific mixed-effects models controlling for participant demographic characteristics. RESULTS: PCS-12 scores over 24 months improved more among participants in the in-person active intervention arm than among control arm participants (P < 0.05, ES = 0.21); there were no other statistically significant treatment arm differences in HRQOL change. Greater weight loss was associated with improvements in most outcomes (P < 0.05 to < 0.0001). CONCLUSIONS: Participants in the in-person active intervention improved more in physical function HRQOL than participants in the control arm did. Greater weight loss during the study was associated with greater improvement in all PRO except for sleep quality, suggesting that weight loss is a key factor in improving HRQOL.

A behavioral weight-loss intervention for persons with serious mental illness in psychiatric rehabilitation centers.

OBJECTIVE: Overweight and obesity are epidemic in populations with serious mental illnesses. We developed and pilot-tested a behavioral weight-loss intervention appropriately tailored for persons with serious mental disorders. METHODS: We conducted a single-arm pilot study in two psychiatric rehabilitation day programs in Maryland, and enrolled 63 overweight or obese adults. The 6-month intervention provided group and individual weight management and group physical activity classes. The primary outcome was weight change from baseline to 6 months. RESULTS: A total of 64% of those potentially eligible enrolled at the centers. The mean age was 43.7 years; 56% were women; 49% were white; and over half had schizophrenia or a schizoaffective disorder. One-third had hypertension and one-fifth had diabetes. In total, 52 (82%) completed the study; others were discharged from psychiatric centers before completion of the study. Average attendance across all weight management sessions was 70% (87% on days participants attended the center) and 59% for physical activity classes (74% on days participants attended the center). From a baseline mean of 210.9 lbs (s.d. 43.9), average weight loss for 52 participants was 4.5 lb (s.d. 12.8) (P<0.014). On average, participants lost 1.9% of body weight. Mean waist circumference change was 3.1 cm (s.d. 5.6). Participants on average increased the distance on the 6-minute walk test by 8%. CONCLUSION: This pilot study documents the feasibility and preliminary efficacy of a behavioral weight-loss intervention in adults with serious mental illness who were attendees at psychiatric rehabilitation centers. The results may have implications for developing weight-loss interventions in other institutional settings such as schools or nursing homes.

Physical activity and physique anxiety in older adults: fitness, and efficacy influences.

Employing a randomized controlled trial, this study documents the effects of six months of physical activity and six month follow-up on reduction in social physique anxiety (SPA) in older adults. In addition, the role played by changes in behavioral, physiological, and psychological predictors of changes in SPA were examined. Participants (n = 174, mean age = 65 yrs) were randomly assigned to one of two activity groups and engaged in a six-month structured exercise program. Measures of physique anxiety were taken at baseline, six and twelve months. Latent growth curve analyses revealed significant reductions in SPA over the course of the 12-month period. Structural analyses controlling for treatment condition indicated that improvements in self-efficacy and fitness were significant predictors of changes in SPA but that changes in body fat and exercise frequency did not contribute to variation in SPA. Overall this model accounted for 19% of the variation in SPA changes. The extent to which changes in SPA may contribute to continued physical activity participation in older adults and how exercise programs might effectively influence predictors of SPA are discussed.

Social relations, physical activity, and well-being in older adults.

BACKGROUND: A randomized controlled trial was conducted to examine: (a) the effect of two physical activity modes on changes in subjective well-being (SWB) over the course of a 12-month period in older, formerly sedentary adults (N = 174, M age = 65.5 years) and (b) the role played by physical activity participation and social support in changes in SWB over time. METHOD: Participants were randomized into either an aerobic activity group or a stretching and toning group. Structural equation modeling was employed to conduct multiple sample latent growth curve analyses of individual growth in measures of SWB (happiness, satisfaction with life, and loneliness) over time. RESULTS: A curvilinear growth pattern was revealed with well-being significantly improving over the course of the intervention followed by significant declines at the 6-month follow-up. Subsequent structural analyses were conducted showing that frequency of exercise participation was a significant predictor of improvement in satisfaction with life, whereas social relations were related to increases in satisfaction with life and reductions in loneliness. Improvements in social relations and exercise frequency also helped to buffer the declines in satisfaction with life at follow-up. CONCLUSIONS: It appears that social relations integral to the exercise environment are significant determinants of subjective well-being in older adults. Findings are discussed in terms of how physical activity environments might be structured to maximize improvements in more global well-being constructs such as satisfaction with life.