There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells ...having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins.
With the use of a multistate, registry-linkage cohort study, BDNCO-embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal tumors included neuroblastoma, nephroblastoma, and hepatoblastoma. Potential HR modification (HRM) was investigated by infant sex, maternal race/ethnicity, maternal age, and maternal education.
The risk of embryonal tumors among those with BDNCOs was 0.09% (co-occurring n = 105) compared to 0.03% (95% CI, 0.03%-0.04%) among those without a birth defect. Children with BDNCOs were 4.2 times (95% CI, 3.5-5.1 times) as likely to be diagnosed with an embryonal tumor compared to children born without a birth defect. BDNCOs were strongly associated with hepatoblastoma (HR, 16.1; 95% CI, 11.3-22.9), and the HRs for neuroblastoma (3.1; 95% CI, 2.3-4.2) and nephroblastoma (2.9; 95% CI, 1.9-4.4) were elevated. There was no notable HRM by the aforementioned factors.
Children with BDNCOs are more likely to develop embryonal tumors compared to children without a birth defect. Disruptions of shared developmental pathways may contribute to both phenotypes, which could inform future genomic assessments and cancer surveillance strategies of these conditions.
Sleep problems are common in children with autism spectrum disorder (ASD), with 40% to 80% prevalence. Common disorders include insomnia, parasomnias, and circadian rhythm sleep-wake disorders. These ...problems have a multifactorial etiology and can both exacerbate and be exacerbated by core ASD symptoms. Sleep problems also impact the health and quality of life of both patients and their caregivers. All children with autism should be regularly screened for sleep problems and evaluated for co-occurring medical contributors. Behavioral interventions with caregiver training remain first-line treatment for sleep disorders in both neurotypical and neurodiverse youth.
Background
Many quality measures in cancer care are process measures. The rates of compliance for these measures over time have not been well described, and the relationships between measure ...compliance and survival are not well understood.
Methods
The National Cancer Database, representing cancer registry data from approximately 1500 Commission on Cancer (CoC) cancer programs, was queried to determine the rates of compliance, with the CoC’s colon cancer quality measure requiring 12 regional lymph nodes be removed at resection. Data were assessed in 2003, before the measure was reported to programs, through 2015. Measure compliance and risk-adjusted survival were examined by hospital type.
Results
From 2003 to 2015, 544,018 cases of colon cancer were analyzed for number of nodes removed. In 2003, compliance was 52.8% and National Cancer Institute (NCI) centers had the highest compliance rate (69.0%), followed by academic cancer centers (61.9%), comprehensive community hospitals (50.9%), and community hospitals (44.0%). Between 2003 and 2015, compliance improved for all hospital types, although differences remained. Risk-adjusted survival in 2009 was better at NCI centers hazard ratio (HR) 0.76 than at academic cancer centers (HR 0.90), which had better survivals than comprehensive community programs (HR 0.93) when compared with patients treated at community hospitals.
Conclusion
After introduction of this quality measure, performance at CoC-accredited hospitals improved over the subsequent 13 years, and survival by hospital type paralleled measure compliance by hospital type. This demonstrated measurement may be associated with improvements in performance, and that there are differences in performance and outcome by hospital type.
For people living with long-term physical disability (LTPD) social participation may involve managing physical impairments and secondary health conditions (SHCs) that are not due to the ...pathophysiology of the LTPD diagnosis itself. Prior research found a negative relationship between SHCs and participation in social roles in people with spinal cord injury (SCI). We expand on this research by investigating the influence of SHCs on participation in social roles for people with one of four LTPDs, controlling for co-variates. We (1) evaluated the associations between SHCs and participation in social roles; and (2) determined whether SHCs on individuals' ability to participate in social roles varies by type of diagnosis in those aging with either SCI, muscular sclerosis, muscular dystrophy, or post-polio syndrome. Cross-sectional, secondary data analysis from a return-by-mail survey. N = 1,573. Data were analyzed with multiple linear regressions (hypothesis 1), and then three moderated regressions (hypothesis 2). After controlling for demographics, SHCs were associated with lower ability to participate in social roles and accounted for 48% of the variance (all p's <.001). The relationship between depression and social role participation was moderated by diagnosis, such that depression was more negatively associated with social participation among individuals with SCI (p = .020). Thus, SHC negatively impact participation in social roles.
Inconsistencies have been reported on the effect of sex on aldosterone (ALDO) levels leading to clinical confusion. The reasons for these inconsistencies are uncertain but include estrogen and/or its ...receptor modulating target gene responses to mineralocorticoid receptor activation and ALDO secretagogues' levels. This study's goal was to determine whether ALDO's biosynthesis also differed by sex. Two approaches were used. First, plasma renin activity and aldosterone were measured in rats. Both were significantly higher in males. Secondly, using rat zona glomerulosa (ZG) cells, we assessed three ex vivo areas: (1) activity/levels of early steps in ALDO's biosynthesis (StAR and CYP11A1); (2) activity/levels of a late step (CYP11B2); and (3) the status of the mineralocorticoid receptor (MR)-mediated, ultrashort feedback loop. Females had higher expression of CYP11A1 and StAR and increased CYP11A1 activity (increased pregnenolone/corticosterone levels) but did not differ in CYP11B2 expression or activity (ALDO levels). Activating the ZG's MR (thereby activating the ultrashort feedback loop) reduced CYP11B2's activity similarly in both sexes. Exvivo, these molecular effects were accompanied, in females, by lower ALDO basally but higher ALDO with angiotensin II stimulation. In conclusion, we documented that not only was there a sex-mediated difference in the activity of ALDO's biosynthesis but also these differences at the molecular level help explain the variable reports on ALDO's circulating levels. Basally, both in vivo and ex vivo, males had higher ALDO levels, likely secondary to higher ALDO secretagogue levels. However, in response to acute stimulation, ALDO levels are higher in females because of the greater levels and/or activity of their StAR/CYP11A1.
The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) surgical risk calculator (SRC) is an open access calculator predicting patients’ risk of postoperative ...complications. This study aims to assess the validity of the SRC in patients undergoing microsurgical free flap reconstruction at an Australian tertiary referral centre.
This is a retrospective cohort study of 200 consecutive patients treated up to November 2020. SRC-predicted rates of postoperative complications and hospital length of stay (LOS) were compared to those observed for the ablative and reconstructive components of the procedure. The performance of the SRC was assessed using Brier scores, area under the receiver operating characteristic (ROC) curve (AUC), and the Hosmer–Lemeshow test.
For both ablative and reconstructive components, the SRC discriminates well for pneumonia and urinary tract infection, and it is calibrated well for readmission and sepsis, but it does not discriminate and calibrate well for any single outcome. SRC-predicted hospital LOS and actual LOS did not correlate well for the reconstructive component, but they correlated strongly for the ablative component.
The SRC is a poor predictor of postoperative complication rates and hospital LOS in patients undergoing head and neck microsurgical reconstruction.
DNA-Catalyzed Reductive Amination Wong, On Yi; Mulcrone, Amanda E.; Silverman, Scott K.
Angewandte Chemie,
December 2, 2011, Letnik:
50, Številka:
49
Journal Article
Recenzirano
Odprti dostop
A new reaction for DNA: DNA is shown to catalyze Ni2+‐dependent reductive amination involving the N2‐amine of a guanosine nucleobase (see picture). This finding expands the repertoire of nucleic acid ...catalysis to include reductive amination, an important natural biosynthetic reaction that has practical synthetic utility.
CCL5 (RANTES (regulated on activation normal T cell expressed and secreted)) and its cognate receptor, CCR5, have been implicated in T cell activation. CCL5 binding to glycosaminoglycans (GAGs) on ...the cell surface or in extracellular matrix sequesters CCL5, thereby immobilizing CCL5 to provide the directional signal. In two CCR5-expressing human T cell lines, PM1.CCR5 and MOLT4.CCR5, and in human peripheral blood-derived T cells, micromolar concentrations of CCL5 induce apoptosis. CCL5-induced cell death involves the cytosolic release of cytochrome c, the activation of caspase-9 and caspase-3, and poly(ADP-ribose) polymerase cleavage. CCL5-induced apoptosis is CCR5-dependent, since native PM1 and MOLT4 cells lacking CCR5 expression are resistant to CCL5-induced cell death. Furthermore, we implicate tyrosine 339 as a critical residue involved in CCL5-induced apoptosis, since PM1 cells expressing a tyrosine mutant receptor, CCR5Y339F, do not undergo apoptosis. We show that CCL5-CCR5-mediated apoptosis is dependent on cell surface GAG binding. The addition of exogenous heparin and chondroitin sulfate and GAG digestion from the cell surface protect cells from apoptosis. Moreover, the non-GAG binding variant, (⁴⁴AANA⁴⁷)-CCL5, fails to induce apoptosis. To address the role of aggregation in CCL5-mediated apoptosis, nonaggregating CCL5 mutant E66S, which forms dimers, and E26A, which form tetramers at micromolar concentrations, were utilized. Unlike native CCL5, the E66S mutant fails to induce apoptosis, suggesting that tetramers are the minimal higher ordered CCL5 aggregates required for CCL5-induced apoptosis. Viewed altogether, these data suggest that CCL5-GAG binding and CCL5 aggregation are important for CCL5 activity in T cells, specifically in the context of CCR5-mediated apoptosis.
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