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Adjuvant and neoadjuvant chemotherapy with regard to osteosarcoma: JCOG Bone fragments and Delicate Muscle Tumour Research Class.
These engineered cells not only have to avoid GVHD but also have to retain their anti-tumor efficacy in vivo. Here, we expand on the recent efforts and strides that have been made in the design and testing of universal allogeneic CAR T cells.AIMS/HYPOTHESIS Evidence of an association between maternal smoking during pregnancy (prenatal smoking) and childhood type 1 diabetes is mixed. Previous studies have been small and potentially biased due to unmeasured confounding. The objectives of this study were to estimate the association between prenatal smoking and childhood type 1 diabetes, assess residual confounding with a negative control design and an E-value analysis, and summarise published effect estimates from a meta-analysis. METHODS This whole-of-population study (births from 1999 to 2013, participants aged ≤15 years) used de-identified linked administrative data from the South Australian Early Childhood Data Project. Type 1 diabetes was diagnosed in 557 children (ICD, tenth edition, Australian Modification [ICD-10-AM] codes E10, E101-E109) during hospitalisation (2001-2014). Families not given financial assistance for school fees was a negative control outcome. Adjusted Cox proportional HRs were calculated. Analyses were conducted on completel smoking and childhood type 1 diabetes, with a HR of 1.67, could negate the observed effect. CONCLUSIONS/INTERPRETATION Our best estimate from the study is that maternal smoking in pregnancy was associated with 16% lower childhood type 1 diabetes incidence, and some of this effect was due to residual confounding.Adolescent risky sexual behaviors can result in negative consequences such as sexually transmitted infection. However, much research effort has been placed on understanding individual characteristics, rather than the role of neighborhood environment. This study addressed the prospective effects of neighborhood and family functioning in preadolescence on risky sexual behaviors. Participants included 4179 youth (Mage = 11.01 years, range 8.64-13.83; 51% female) and their caregivers. Using objective and self-reported measures of neighborhood and family functioning, results from multilevel regression analyses indicated that youth residing in disordered neighborhoods or had poorer family functioning in preadolescence were more likely to initiate sexual intercourse at younger ages 5 years later. Specifically, neighborhood poverty and decay were linked to early sexual initiation, whereas neighborhood social and family processes were protective against early sexual initiation. Males were more likely to engage in risky sexual behaviors in neighborhoods with greater poverty or decay; neighborhood poverty was linked with sexual initiation in White but not African American youth. Finally, parental monitoring moderated relationships between neighborhood social resources and contraceptive use, with neighborhood social resources linked with greater contraceptive use at low levels of parental monitoring, but lower contraceptive use at high levels of parental monitoring. These findings underscore the importance of neighborhood and family contexts in adolescents' risky sexual behavior, suggesting that males and White youth are more vulnerable to the effects of neighborhood poverty and that more research is needed on the possible counterproductive function of parental monitoring in neighborhoods with greater social resources.The original article was published with an incorrect license statement.The original article has published with incorrect license statement.PURPOSE The pleiotropic roles of phosphodiesterase-5 inhibitors (PDE5is) in cardiovascular diseases have attracted attention. The effect of vardenafil (a PDE5i) is partly mediated through reduced oxidative stress, but it is unclear whether vardenafil protects against hydrogen peroxide (H2O2)-induced endothelial cell injury, and the molecular mechanisms that are involved remain unknown. We determined the protective role of vardenafil on H2O2-induced endothelial cell injury in cultured human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS Vardenafil decreased the number of TUNEL-positive cells, increased the Bcl2/Bax ratio, and ameliorated the numbers of BrdU-positive cells in H2O2-treated HUVECs. The bone morphogenetic protein receptor (BMPR)/p-Smad/MSX2 pathway was enhanced in response to H2O2, and vardenafil treatment could normalize this pathway. To determine whether the BMP pathway is involved, we blocked the BMP pathway using dorsomorphin, which abolished the protective effects of vardenafil. We found that vardenafil improved the H2O2-induced downregulation of BMP-binding endothelial regulator protein (BMPER), which possibly intersects with the BMP pathway in the regulation of endothelial cell injury in response to oxidative stress. CONCLUSIONS We demonstrated for the first time that exogenous H2O2 activates BMPR expression and promotes Smad1/5/8 phosphorylation. Additionally, vardenafil can attenuate H2O2-induced endothelial cell injury in HUVECs. Vardenafil decreases apoptosis through an improved Bcl-2/Bax ratio and increases cell proliferation. Vardenafil protects against endothelial cell injury through ameliorating the intracellular oxidative stress level and BMPER expression. The protective role of vardenafil on H2O2-induced endothelial cell injury is mediated through BMPR/p-Smad/MSX2 in HUVECs.PURPOSE The usefulness and mechanisms of antiarrhythmic drug (AAD) pre-treatment as a facilitator of the acute success of electrical cardioversion (ECV) in atrial fibrillation (AF) remain controversial. We sought to analyze the role of AAD treatment with this purpose, differentiating its possible utility either facilitating the restoration of sinus rhythm (SR) or reducing immediate AF recurrences (IAFR). check details METHODS We analyzed 2962 consecutive patients with persistent AF undergoing ECV prospectively included in 3 national registries. The acute success of ECV was indicated by the reversion to SR without presenting an IAFR ( less then  2 h). RESULTS A total of 1410 patients (48%) received AAD treatment prior to ECV (80% amiodarone, 15% class Ic AAD, 2% other AAD). The rate of restoration of SR was similar between the patients treated with amiodarone (92%), class Ic AAD (91%) and who did not receive AAD pre-treatment (91%) (p = 0.92). However, those treated with amiodarone had fewer IAFR than those in the other two groups (amiodarone 3% vs class Ic 7% vs without treatment 6%; p = 0.
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