Short-Term Intravenous Administration of Carbon Nano-Onions is Non-Toxic in Female Mice.

Background: A nanoscale drug carrier could have a variety of therapeutic and diagnostic uses provided that the carrier is biocompatible in vivo. Carbon nano-onions (CNOs) have shown promising results as a nanocarrier for drug delivery. However, the systemic effect of CNOs in rodents is unknown. Therefore, we investigated the toxicity of CNOs following intravenous administration in female BALB/c mice. Results: Single or repeated administration of oxi-CNOs (125, 250 or 500 µg) did not affect mouse behavior or organ weight and there was also no evidence of hepatotoxicity or nephrotoxicity. Histological examination of organ slices revealed a significant dose-dependent accumulation of CNO aggregates in the spleen, liver and lungs (p<0.05, ANOVA), with a trace amount of aggregates appearing in the kidneys. However, CNO aggregates in the liver did not affect CYP450 enzymes, as total hepatic CYP450 as well as CYP3A catalytic activity, as meased by erythromycin N-demethylation, and protein levels showed no significant changes between the treatment groups compared to vehicle control. CNOs also failed to act as competitive inhibitors of CYP3A in vitro in both mouse and human liver microsomes. Furthermore, CNOs did not cause oxidative stress, as indicated by the unchanged malondialdehyde levels and superoxide dismutase activity in liver microsomes and organ homogenates. Conclusion: This study provides the first evidence that short-term intravenous administration of oxi-CNOs is non-toxic to female mice and thus could be a promising novel and safe drug carrier.

Use of a Mobile Lifestyle Intervention App as an Early Intervention for Adolescents With Obesity: Single-Cohort Study.

BACKGROUND: Effective, resource-efficient treatment is urgently needed to address the high rates of pediatric and adolescent obesity. This need has been accelerated by the COVID-19 pandemic. The use of a mobile health tool as an early intervention before a clinic-based multidisciplinary weight management program could be an effective treatment strategy that is appropriate during a pandemic. OBJECTIVE: This study aims to assess the effectiveness of and adolescent engagement with a mobile app-based lifestyle intervention program as an early intervention before enrollment in a clinic-based multidisciplinary weight management program. METHODS: This prospective single-cohort study involved adolescents, aged 10-16 years, who were overweight and obese (defined as BMI percentile above the 85th percentile). Participants used the mobile Kurbo app as an early intervention before enrolling in a clinic-based multidisciplinary weight management program. Kurbo's health coaches provided weekly individual coaching informed by a model of supportive accountability via video chat, and participants self-monitored their health behavior. The implementation of Kurbo as an early intervention was evaluated using the reach, effectiveness, adoption, implementation, and maintenance framework by reach (number who consented to participate out of all patients approached), implementation (Kurbo engagement and evaluation), and effectiveness as measured by the primary outcome of the BMI z-score at 3 months. Secondary outcome measures included changes in body fat percentage, nutrition and physical activity levels, and quality of life at 3 months. Maintenance was defined as the outcome measures at 6-month follow-up. RESULTS: Of the 73 adolescents who were approached for enrollment, 40 (55%) of adolescents were recruited. The mean age was 13.8 (SD 1.7) years, and the mean BMI z-score was 2.07 (SD 0.30). In the multiethnic Asian sample, 83% (33/40) of the participants had household incomes below the national median. Kurbo engagement was high, with 83% (33/40) of participants completing at least 7 coaching sessions. In total, 78% (18/23) of participants rated the app as good to excellent and 70% (16/23) stated that they would recommend it to others. There were no statistically significant changes in BMI z-scores at 3 months (P=.19) or 6 months (P=.27). Participants showed statistically significant improvements in measured body fat percentage, self-reported quality of life, and self-reported caloric intake from the 3-day food diaries at 3 and 6 months. CONCLUSIONS: The use of Kurbo before enrollment in an outpatient multidisciplinary clinical care intervention is a feasible strategy to expand the reach of adolescent obesity management services to a low-income and racially diverse population. Although there was no significant change in BMI z-scores, the use of Kurbo as an early intervention could help to improve quality of life and reduce body fat percentage and total caloric intake.

Electron Transfer Quenching of Rhodamine 6G by N-Methylpyrrole Is an Unproductive Process in the Photocatalytic Heterobiaryl Cross-Coupling Reaction.

In the heterobiaryl cross-coupling reaction between aryl halides (Ar-X) and N-methylpyrrole (N-MP) catalyzed by rhodamine 6G (Rh6G+) under irradiation with visible light, a highly active and long-lived (millisecond time range) rhodamine 6G radical (Rh6G•) is formed upon electron transfer from N,N-diisopropylethylamine (DIPEA) to Rh6G+. In this study, we utilized steady-state and time-resolved spectroscopy techniques to demonstrate the existence of another electron-transfer process occurring from the relatively electron-rich N-MP to photoexcited Rh6G+ that was neglected in the previous reports. In this case, the radical Rh6G• formed is short-lived and undergoes rapid recombination (nanosecond time-range), rendering it ineffective in reducing Ar-X to aryl radicals Ar• that can subsequently be trapped by N-MP. This is further demonstrated via two model reactions involving 4'-bromoacetophenone and 1,3,5-tribromobenzene with insignificant product yields after visible-light irradiation in the absence of DIPEA. The unproductive quenching of photoexcited Rh6G+ by N-MP leads to a lower concentration of photocatalyst available for competitive charge transfer with DIPEA and hence decreases the efficiency of the cross-coupling reaction.

Effect of disaccharide-polyol systems on the thermal stability of freeze-dried Mycobacterium bovis.

Live attenuated Mycobacterium bovis (M. bovis), marketed as Bacille Calmette-Guérin is the only FDA-approved vaccine against tuberculosis. The prerequisite of cold chain storage between 2 and 8 °C hinders the global vaccination effort. The study aims to investigate the effect of trehalose, sucrose and glycerol combinations in enhancing the stability of M. bovis. The bacilli were formulated in various ratios of trehalose-glycerol, sucrose-glycerol, trehalose-sucrose-glycerol systems (test samples) and sodium glutamate (control), freeze-dried and stored for 28 days at 4 °C, 25 °C and 37 °C. Bacteria viability at pre-, post-freeze-drying and after storage were quantified by its density in colony-forming unit per milliliter (CFU/mL) as obtained through the pour plate method. Formulations were characterized using differential scanning calorimetry. Structural collapsed cakes were found on all freeze-dried formulations because of the low Tg'. Comparing between binary and ternary formulations, trehalose-sucrose-glycerol was found to be a superior lyoprotectant. Upon storage, the viability of bacteria in disaccharide-polyol formulations was highest when stored at 4 °C followed by 25 °C. The lowest viability was found after storage at 37 °C. While the ternary disaccharide-polyol system may be used as a thermoprotectant up to 25 °C, sodium glutamate has a superior thermoprotective effect at temperature above 25 °C.

[Effects of the lipid-lowering drugs on endothelial hyperplasia in inferior vena cava grafts in dogs].

OBJECTIVE: To investigate the effects of the lipid-lowering drugs in alleviating endothelial hyperplasia in the inferior vena cava (IVC) grafts in dogs. METHODS: The Dacron grafts seeded with autologous venous fragments were implanted into the IVC of 20 dogs, including 12 dogs receiving oral lipid-lowering drugs serving as the treatment group and the other 8 without medication as the control group. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-ch) and high-density lipoprotein cholesterol (HDL-ch) in the serum were measured regularly, and all the grafts harvested to measure the thickness of the endothelium. RESULTS: The total patency rate of the IVC were higher in the treatment group (75%) than in the control group (37.5%), and new endothelial lining was formed two weeks after the operation. Compared with the control group, the endothelial thickness of the grafts at the proximal (P<0.01), middle (P<0.05) and distal segments (P<0.05) of the IVC were all smaller in the treatment group, which also had lower serum LDL-ch and TC levels (both P<0.05) but with comparable HDL-ch levels (P>0.05). CONCLUSION: Administration of lipid-lowering drugs may reduce the level of serum LDL-ch and TC and the endothelial thickness of the grafts to improve the patency rate of the vessels.