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Sexton Adcock posted an update 6 months, 2 weeks ago
In this review, we highlight the design and construction of conceptually interesting and clinically viable actively targeted cancer nanomedicines containing small molecular drugs, nucleic acid drugs, or protein/peptide drugs, discuss their pros and cons, and give perspectives on the future developments and clinical translation. We are convinced that with collaborative research and development across the disciplines, actively targeted cancer nanomedicines will make a breakthrough and become an indispensable platform for precision cancer therapy.
Transcranial focused ultrasound and microbubble (FUS+MB) exposure enables targeted, noninvasive drug delivery to the brain. Given the protective nature of the blood-brain barrier (BBB), the development of sonication strategies that maximize therapeutic efficacy while minimizing the risk of tissue damage are essential. This work aimed to compare the safety of 10ms tone bursts, widely used in the field, to a recently described rapid short-pulse (RaSP) sequence, while accounting for drug delivery potential.
Forty-one male wild-type mice received FUS+MB exposure (1.78MHz driving frequency; 0.5Hz burst repetition frequency; 250s duration; 40μl/kg Definity) at a range of fixed pressure amplitudes. A RaSP sequence (13 five-cycle pulses/10ms burst) was compared to 10ms tone bursts (B10). For animals in cohort #1 (n=26), T1 mapping was used to quantify gadobutrol extravasation. Three targets, temporarily separated by 10min, were sonicated in each brain to compare the time dependence of BBB permeability enhancementy enhancement, and thus the potential for drug delivery, the RaSP sequence tested here did not produce measurable improvements over the B10 sequence and may present an increased risk of vascular damage.
When accounting for the magnitude of BBB permeability enhancement, and thus the potential for drug delivery, the RaSP sequence tested here did not produce measurable improvements over the B10 sequence and may present an increased risk of vascular damage.In one experiment with human participants, we investigated the effects of using multiple contexts during extinction on the renewal of operant responses. Undergraduate students played a videogame in which they learned to shoot at enemies in Context A. Then, all participants experienced an extinction training. For half of the participants, extinction trials were conducted in a single context, whereas the other half received extinction in three different contexts. Finally, all participants were tested in Context A. We observed that conducting extinction in multiple contexts attenuated ABA renewal. The present results suggest that conducting extinction in multiple contexts can be used as a behavioral technique to reduce operant renewal.There is solid evidence for an association between physical activity and metabolic health outcomes in children and youth, but for methodological reasons most studies describe the intensity spectrum using only a few summary measures. We aimed to determine the multivariate physical activity intensity signature associated with metabolic health in a large and diverse sample of children and youth, by investigating the association pattern for the entire physical intensity spectrum. We used pooled data from 11 studies and 11,853 participants aged 5.8-18.4 years included in the International Children’s Accelerometry Database. We derived 14 accelerometry-derived (ActiGraph) physical activity variables covering the intensity spectrum (from 0-99 to ≥8000 counts per minute). To handle the multicollinearity among these variables, we used multivariate pattern analysis to establish the associations with indices of metabolic health (abdominal fatness, insulin sensitivity, lipid metabolism, blood pressure). A composite metabolic health score was used as the main outcome variable. Associations with the composite metabolic health score were weak for sedentary time and light physical activity, but gradually strengthened with increasing time spent in moderate and vigorous intensities (up to 4000-5000 counts per minute). Association patterns were fairly consistent across sex and age groups, but varied across different metabolic health outcomes. This novel analytic approach suggests that vigorous intensity, rather than less intense activities or sedentary behavior, are related to metabolic health in children and youth.This comparative effectiveness trial compared the longer-term effectiveness (12 and 18 months) of the standard Fit & Strong! physical activity program to Fit & Strong! Plus, which combined physical activity and dietary weight loss. Outcomes were weight, diet quality, physical activity, osteoarthritis symptoms, performance measures, and anxiety/depression. learn more In this study, 413 overweight/obese participants with OA, ≥60 years old and primarily African American, were randomly assigned to Fit & Strong! (F&S!) or Fit & Strong! Plus (F&S! Plus), with outcomes assessed at 2, 6, 12, and 18 months. 356 (86%) participants completed the 18-month visit. Compared with participants randomized to standard F&S!, F&S! Plus participants maintained longer-term benefits at 12 months in weight (mean change ± SE -1.7 ± 0.3 kg for F&S! Plus vs -0.9 ± 0.3 kg for F&S!, p = 0.049), BMI (-0.6 ± 0.1 vs -0.3 ± 0.1 kg/m2, p = 0.04), waist circumference (-2.7 ± 0.6 vs -0.4 ± 0.6 cm, p = 0.004), and lower extremity strength (1.6 ± 0.2 vs 1.0 ± 0.2 chair stands, p = 0.046). At 18 months, F&S! Plus participants showed improved lower extremity strength (1.4 ± 0.2 vs. 0.7 ± 0.2 chair stands, p = 0.045. African American older adults in the F&S! Plus arm showed sustained modest improvements in weight, waist circumference, and lower extremity strength at 12 months and in lower extremity strength at 18 months compared to F&S!. Implications for the translation of evidence-based programs into community settings to support healthy behaviors in older adults are discussed.This study examined the association between measures of acculturation to the US environment including place of birth, and language spoken at home and proportion of life in the US among foreign-born, in relation to the dietary contribution of ultra-processed foods. Ultra-processed foods, as defined by the NOVA food classification system, are formulations of macronutrients (starches, sugars, fats and protein isolates) with little, if any, whole food and often with added flavors, colors, emulsifiers and other cosmetic additives. We studied 14,663 participants from the National Health and Nutrition Examination Survey 2011-2016, aged 20+ years, who completed a 1-day 24-h dietary recall. Food items were classified using NOVA into ultra-processed or non-ultra-processed foods. Linear regression models adjusted for age, sex, family income, education and race/ ethnicity, showed significant associations between general acculturation measures and dietary contribution of ultra-processed foods. Foreign-born adults consumed less ultra-processed foods than US-born adults (45 vs.