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55 vs 3.76, P < .001; 3.55 vs 3.80, P= .001; 3.55 vs 3.99, P < .001). The pediatric asthma impact survey scores improved from baseline to visits 2 and 3 (43.33 vs 34.08, P < .001; 43.33 vs 31.74, P < .001). ED visits and prednisone use significantly decreased from baseline to visits 2 and 3 (ED 0.46 vs 0.13, P= .03; 0.46 vs 0.02, P= .02; prednisone use, 0.49 vs 0.13, P= .02; 0.49 vs 0.03, P= .003. Satisfaction was high with mean client satisfaction questionnaire score of approximately 30 (out of 32) at all visits.
ASTHMAXcel Adventures improved asthma control, knowledge, and quality of life, and reduced ED visits and prednisone use with high satisfaction scores.
ASTHMAXcel Adventures improved asthma control, knowledge, and quality of life, and reduced ED visits and prednisone use with high satisfaction scores.
Previously, we found that reported infant rhinorrhea and watery eyes without a cold (RWWC) predicted school age exercise-induced wheezing, emergency department visits, and respiratory-related hospitalizations for asthma. These findings appeared independent of infant wheezing and allergy. Overall, we theorize that prenatal material hardship and psychosocial distress can induce infant dysregulation in the autonomic nervous system leading to infant RWWC and school age exercise-induced wheezing.
To test the hypotheses that indicators of prenatal stress and measures of maternal demoralization, which can alter infant autonomic nervous system responses, would predict infant RWWC.
In a prospective birth cohort of urban children (n= 578), pregnant women were queried in the third trimester about material hardship and maternal demoralization using validated instruments. Child RWWC was queried every 3 months in infancy.
Notably, 44% of the mothers reported not being able to afford at least one of the basic needs of daily living during pregnancy, and children of those mothers were more likely to have infant RWWC (P < .001). The children had an increased risk of RWWC with increasing maternal demoralization during pregnancy (P < .001). In models controlling for sex, race and ethnicity, maternal asthma, maternal allergy, smoker in the home (pre- or postnatal), prenatal pesticide exposure, and older siblings, RWWC was predicted by mother's report of material hardship (relative risk, 1.22; P= .021) and maternal demoralization (relative risk, 1.14; P= .030).
These results suggest an association between material hardship and psychological distress during pregnancy and RWWC in infancy, further supporting a link between infant autonomic dysregulation and RWWC.
These results suggest an association between material hardship and psychological distress during pregnancy and RWWC in infancy, further supporting a link between infant autonomic dysregulation and RWWC.The CRISPR/Cas9 system is an efficient genome-editing system that has been successfully applied in the field of gene therapy. However, clinical applications of the CRISPR/Cas9 system are limited by the delivery method and safety concerns. Extracellular Vesicles (EVs) can be released from almost every type of cell, and they act as shuttles to convey molecules between cells. Here, we used EVs derived from epithelial cells as a biosafety delivery platform for the CRISPR/Cas9 system and modified the EVs with a chimeric-antigen receptor (CAR) to give them selective tropism to tumors. Compared to normal EVs, CAR-EVs accumulated in cancer tumors rapidly and released the CRISPR/Cas9 system targeting the MYC oncogene efficiently, both in vitro and in vivo. Taken together, the combination of EV and CAR was confirmed to be a novel strategy facilitating the use of natural gene therapy platforms in cancer treatment in this proof-of-concept research.Neuroblastoma is the most commonly diagnosed extracranial solid tumor in children. The patients with aggressive metastatic disease or refractory/relapsed neuroblastoma currently face a dismally low chance of survival. Thus, there is a great need for more effective therapies for this illness. In previous studies, we, as well as others, showed that the immune cell chemoattractant C-C motif chemokine ligand 21 (CCL21) is effective as an intratumoral therapy able to slow the growth of cancers. In this current study, we developed and tested an injectable, slow-release, uniform, and optimally loaded alginate nanoformulation of CCL21 as a means to provide prolonged intratumoral treatment. The alginate-nanoformulated CCL21, when injected intratumorally into mice bearing neuroblastoma lesions, significantly prolonged survival and decreased the tumor growth rate compared to CCL21 alone, empty nanoparticles, or buffer. Notably, we also observed complete tumor clearance and subsequent full protection against tumor rechallenge in 33% of nanoformulated CCL21-treated mice. Greater intratumoral presence of nanoformulated CCL21, compared to free CCL21, at days 1 and 2 after treatment ended was confirmed through fluorescent labeling and tracking. Nanoformulated CCL21-treated tumors exhibited a general pattern of prolonged increases in anti-tumor cytokines and relatively lower levels of pro-tumor cytokines in comparison to tumors treated with CCL21 alone or buffer only. https://www.selleckchem.com/products/frax486.html Thus, this novel nanoformulation of CCL21 is an effective treatment for neuroblastoma, and may have potential for the delivery of CCL21 to other types of solid tumors in the future and as a slow-release delivery modality for other immunotherapies.Bile acids are synthesized in the liver, stored in the gallbladder, and secreted into the duodenum at meals. Apical sodium-dependent bile acid transporter (ASBT), an ileal Na+-dependent transporter, plays the leading role of bile acid absorption into enterocytes, where bile acids are delivered to basolateral side by ileal bile acid binding protein (IBABP) and then released by organic solute transporter OSTα/β. The absorbed bile acids are delivered to the liver via portal vein. In this process called "enterohepatic recycling", only 5% of the bile acid pool (~3 g in human) is excreted in feces, indicating the large recycling capacity and high transport efficacy of ASBT-mediated absorption. Therefore, bile acid transporter-mediated oral drug delivery has been regarded as a feasible and potential strategy to improve the oral bioavailability. This review introduces the key factors in enterohepatic recycling, especially the mechanism of bile acid uptake by ASBT, and the development of bile acid-based oral drug delivery for ASBT-targeting, including bile acid-based prodrugs, bile acid/drug electrostatic complexation and bile acid-containing nanocarriers.