Currently, there is no effective treatment for placental dysfunction in utero. In a ligated mouse model of fetal growth restriction (FGR), nanoparticle-mediated human insulin-like 1 growth factor (hIGF1) gene delivery (NP-Plac1-hIGF1) increased hIGF1 expression and maintained fetal growth. However, whether it can restore fetal growth remains to be determined. Using the endothelial nitric oxide synthase knockout (eNOS-/-) mouse model, a genetic model of FGR, we found that despite inducing expression of hIGF1 in the placentas treated with NP-Plac1-hIGF1 (P = 0.0425), FGR did not resolve. This was associated with no change to the number of fetal capillaries in the placental labyrinth; an outcome which was increased with NP-Plac1-hIGF1 treatment in the ligated mouse model, despite increased expression of angiopoietin 1 (P = 0.05), and suggested IGF1 signaling in the placenta requires eNOS to modulate placenta angiogenesis. To further assess this hypothesis, BeWo choriocarcinoma cell line and human placental explant cultures were treated with NP-Plac1-hIGF1, oxidative stress was induced with hydrogen peroxide (H2O2), and NOS activity was inhibited using the inhibitor NG-monomethyl-l-arginine (l-NMMA). In both BeWo cells and explants, the protective effect of NP-Plac1-hIGF1 treatment against H2O2-induced cell death/lactate dehydrogenase release was prevented by eNOS inhibition (P = 0.003 and P less then 0.0001, respectively). This was associated with an increase in mRNA expression of oxidative stress markers hypoxia inducing factor 1α (HIF1α; P less then 0.0001) and ADAM10 (P = 0.0002) in the NP-Plac1-hIGF1 + H2O2 + l-NMMA-treated BeWo cells. These findings show for the first time the requirement of eNOS/NOS in IGF1 signaling in placenta cells that may have implications for placental angiogenesis and fetal growth.Bimodal bilinguals are hearing individuals fluent in a sign and a spoken language. Can the two languages influence each other in such individuals despite differences in the visual (sign) and vocal (speech) modalities of expression? We investigated cross-linguistic influences on bimodal bilinguals' expression of spatial relations. Unlike spoken languages, sign uses iconic linguistic forms that resemble physical features of objects in a spatial relation and thus expresses specific semantic information. Hearing bimodal bilinguals (n = 21) fluent in Dutch and Sign Language of the Netherlands and their hearing nonsigning and deaf signing peers (n = 20 each) described left/right relations between two objects. Bimodal bilinguals expressed more specific information about physical features of objects in speech than nonsigners, showing influence from sign language. They also used fewer iconic signs with specific semantic information than deaf signers, demonstrating influence from speech. Bimodal bilinguals' speech and signs are shaped by two languages from different modalities.Hispanics have a lower burden of heart disease than would be predicted from their risk factors. Explanations for this phenomenon, the Hispanic paradox, focus on specific characteristics of the culture that affect stress appraisal and accumulation, including social connections. Features of culture evolve in the context of language, which influences the way emotions are appraised and expressed. selleck chemicals The Spanish language, a unifying component defining Hispanic cultures, has unique features that may promote emotional expression, expand the emotional concepts implicated in the construction of emotion, and influence the appraisal of stress. Under chronic stress conditions, sustained responses can become maladaptive, leading to disease. Features of the Spanish language allow its speakers a wide range of emotion schemas by virtue of its emotion lexicon, the ability to easily minimize or exaggerate expressions, and ease in considering hypothetical situations with the use of the subjunctive. The hypothesis here proposes that the Spanish language is directly and indirectly (via culture) responsible for mitigating some of the effects of acute stress responses in Hispanics and, therefore, limits stress accumulation and is partly responsible for the Hispanic paradox.Moral reasoning is an essential part of how humans develop and a fundamental aspect of how human societies change over time. On a developmental timescale, reasoning about interpersonal disagreements and dilemmas spurs age-related changes in moral judgments from childhood to adulthood. When asked to distribute resources among others, even young children strive to balance competing concerns with equality, merit, and need. Over the course of development, reasoning and judgments about resource distribution and other moral issues become increasingly sophisticated. From childhood to adulthood, individuals not only evaluate acts as right or wrong but also take the extra steps to rectify inequalities, protest unfair norms, and resist stereotypic expectations about others. The development of moral reasoning also enables change on a societal timescale. Across centuries and communities, ordinary individuals have called for societal change based on moral concerns with welfare, rights, fairness, and justice. Individuals have effectively employed reasoning to identify and challenge injustices. In this article, we synthesize recent insights from developmental science about the roles of moral reasoning in developmental and societal change. In the concluding section, we turn to questions for future research on moral reasoning and change.Introduction World Health Organization has recommended that in healthy persons with category III exposures, who receive wound care and rabies immunoglobulin infiltration, a vaccine regimen consisting of 4 doses administered intramuscularly on days 0, 3, 7, and 14 can be used as an alternative to the 5-dose intramuscular regimen.Objective To assess the clinical safety and immunogenicity of rabies vaccine administered as 4-dose Essen intramuscular regimen for post-exposure prophylaxis.Methods A non-randomized, comparative, controlled study was conducted at the anti-rabies clinic, KIMS Hospital and Research Center, Bangalore, India. The study subjects were divided into study group i.e., 4-dose intramuscular regimen, and control group i.e., 5-dose intramuscular regimen, and were given post-exposure prophylaxis. All subjects were followed for any adverse drug events. Rabies virus neutralizing antibodies was determined on day 14, 90 & 180 at the WHO collaborating center, NIMHANS, Bangalore, India to assess the immunogenicity.