The author of the Acts of the Apostles uses criteria commonly employed in his cultural context to legitimate the Jesus movement and the extension of the mission to the Gentiles as the divine plan. ...While these literary strategies result in material that can be employed uncritically and tragically to serve a bias against the Jewish people, a far more fruitful transposition of the Lukan strategies would raise intelligent questions about the ways of God in the world and the cooperation of humans with those ways.
There is a variability regarding timing of consent and personnel used in patient recruitment for neonatal research. We explored the associations between the study personnel and timing of consent with ...parents' decisional conflict and ultimately their decision to enroll.
This was a multi-site, cross-sectional survey conducted between August 2015 and October 2017. Participants were parents approached to enroll their 24-28-week infant in a clinical trial. Parents completed an interviewer-administered 61-item questionnaire.
Overall, 163 surveys were completed; 105 by parents of enrolled infants and 58 by parents of non-enrolled infants (54.5% participation rate). Neither the individual requesting nor timing of consent was associated with parents' knowledge score, decisional conflict, or decision to enroll. Parents preferred to be approached prenatally and by their infant's doctor.
Study designers and IRBs may allow flexibility in personnel and timing of consent as it is respectful of parents and may enhance trial enrollment.
...M. takes a welcome step by suggesting how the understanding of the cross in John can contribute to contemporary Christian spirituality, which tends toward an overemphasis on the cross as only a ...place of torture, sin, and death.
Oxidized phospholipids (OxPL) are ubiquitous, are formed in many inflammatory tissues, including atherosclerotic lesions, and frequently mediate proinflammatory changes
. Because OxPL are mostly the ...products of non-enzymatic lipid peroxidation, mechanisms to specifically neutralize them are unavailable and their roles in vivo are largely unknown. We previously cloned the IgM natural antibody E06, which binds to the phosphocholine headgroup of OxPL, and blocks the uptake of oxidized low-density lipoprotein (OxLDL) by macrophages and inhibits the proinflammatory properties of OxPL
. Here, to determine the role of OxPL in vivo in the context of atherogenesis, we generated transgenic mice in the Ldlr
background that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter. E06-scFv was secreted into the plasma from the liver and macrophages, and achieved sufficient plasma levels to inhibit in vivo macrophage uptake of OxLDL and to prevent OxPL-induced inflammatory signalling. Compared to Ldlr
mice, Ldlr
E06-scFv mice had 57-28% less atherosclerosis after 4, 7 and even 12 months of 1% high-cholesterol diet. Echocardiographic and histologic evaluation of the aortic valves demonstrated that E06-scFv ameliorated the development of aortic valve gradients and decreased aortic valve calcification. Both cholesterol accumulation and in vivo uptake of OxLDL were decreased in peritoneal macrophages, and both peritoneal and aortic macrophages had a decreased inflammatory phenotype. Serum amyloid A was decreased by 32%, indicating decreased systemic inflammation, and hepatic steatosis and inflammation were also decreased. Finally, the E06-scFv prolonged life as measured over 15 months. Because the E06-scFv lacks the functional effects of an intact antibody other than the ability to bind OxPL and inhibit OxLDL uptake in macrophages, these data support a major proatherogenic role of OxLDL and demonstrate that OxPL are proinflammatory and proatherogenic, which E06 counteracts in vivo. These studies suggest that therapies inactivating OxPL may be beneficial for reducing generalized inflammation, including the progression of atherosclerosis, aortic stenosis and hepatic steatosis.
Objective:
Depression is prevalent among adolescents, affecting about 11% of the United States population ages 12-17. It is therefore pertinent to better understand the factors associated with ...adolescent depression in order to prevent the development of symptoms and minimise negative psychosocial and developmental outcomes.
Methods:
We utilised a self-report survey among 84 adolescents to examine the associations between reassurance seeking, empathy, cognitive coping strategies, and depressive symptoms, among high-school students.
Results:
Female sex and high reassurance seeking were significantly associated with depressive symptoms.
Discussion:
Our study suggests that regular screening for reassurance seeking and depressive symptoms among adolescents, as well as ongoing psychosocial education for parents, teachers, and administrators, may help to identify those in need of intervention.
The Management of Myelomeningocele Study (MOMS) was a multicenter randomized trial comparing the safety and efficacy of prenatal and postnatal closure of myelomeningocele. The trial was stopped early ...because of the demonstrated efficacy of prenatal surgery, and outcomes on 158 of 183 pregnancies were reported. Here, the authors update the 1-year outcomes for the complete trial, analyze the primary and related outcomes, and evaluate whether specific prerandomization risk factors are associated with prenatal surgery benefit.
The primary outcome was a composite of fetal loss or any of the following: infant death, CSF shunt placement, or meeting the prespecified criteria for shunt placement. Primary outcome, actual shunt placement, and shunt revision rates for prenatal versus postnatal repair were compared. The shunt criteria were reassessed to determine which were most concordant with practice, and a new composite outcome was created from the primary outcome by replacing the original criteria for CSF shunt placement with the revised criteria. The authors used logistic regression to estimate whether there were interactions between the type of surgery and known prenatal risk factors (lesion level, gestational age, degree of hindbrain herniation, and ventricle size) for shunt placement, and to determine which factors were associated with shunting among those infants who underwent prenatal surgery.
Ninety-one women were randomized to prenatal surgery and 92 to postnatal repair. The primary outcome occurred in 73% of infants in the prenatal surgery group and in 98% in the postnatal group (p < 0.0001). Actual rates of shunt placement were only 44% and 84% in the 2 groups, respectively (p < 0.0001). The authors revised the most commonly met criterion to require overt clinical signs of increased intracranial pressure, defined as split sutures, bulging fontanelle, or sunsetting eyes, in addition to increasing head circumference or hydrocephalus. Using these modified criteria, only 3 patients in each group met criteria but did not receive a shunt. For the revised composite outcome, there was a difference between the prenatal and postnatal surgery groups: 49.5% versus 87.0% (p < 0.0001). There was also a significant reduction in the number of children who had a shunt placed and then required a revision by 1 year of age in the prenatal group (15.4% vs 40.2%, relative risk 0.38 95% CI 0.22-0.66). In the prenatal surgery group, 20% of those with ventricle size < 10 mm at initial screening, 45.2% with ventricle size of 10 up to 15 mm, and 79.0% with ventricle size ≥ 15 mm received a shunt, whereas in the postnatal group, 79.4%, 86.0%, and 87.5%, respectively, received a shunt (p = 0.02). Lesion level and degree of hindbrain herniation appeared to have no effect on the eventual need for shunting (p = 0.19 and p = 0.13, respectively). Similar results were obtained for the revised outcome.
Larger ventricles at initial screening are associated with an increased need for shunting among those undergoing fetal surgery for myelomeningocele. During prenatal counseling, care should be exercised in recommending prenatal surgery when the ventricles are 15 mm or larger because prenatal surgery does not appear to improve outcome in this group. The revised criteria may be useful as guidelines for treating hydrocephalus in this group.
Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca
2+ mobilization and Erk kinase activation and impair both positive and negative thymic selection.
Itk
−/−
and
Rlk
...−/−Itk
−/−
mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless, we find that CD8 single-positive (SP) thymocytes and peripheral CD8
+ T cells in these mice do not resemble conventional CD8
+ T cells. Instead, these cells express memory markers, rapidly produce interferon-γ, and can be selected on hematopoietically derived cells, similar to MHC class Ib-restricted “innate-type” lymphocytes. Itk deficiency also greatly increases the number of cells selected by MHC class Ib. Expression of a hypersensitive Erk2 mutant partially corrects the CD8
+ T cell phenotypes in
Itk
−/−
mice, arguing that altered signaling permits development of this innate-type CD8
+ cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes.
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