The Influence Of Maternal Infections On Congenital Heart Defect

ABSTRACT Congenital heart defects (CHDs) contribute significantly to heightened infant mortality rates. This review explores the intricate link between maternal infections and CHDs, emphasizing diverse factors influencing fetal development, such as bacterial, fungal, protozoan and viral agents. These infections pose reproductive health risks, potentially leading to complications like prematurity, stillbirth and heart defect to the fetus. The TORCH acronym (Toxoplasma, Other infections, Rubella, Cytomegalovirus, Herpes simplex) identifies infectious teratogens related to congenital issues, emphasizing vertical transmission through the placenta or ascending from the vagina. Rubella and Cytomegalovirus play a significant role in heart defects, particularly when maternal infections amplify CHD risk during pregnancy. Specific scrutiny is placed on Rubella and Cytomegalovirus for their impact on pregnancy outcomes and potential links to congenital heart defects, with preventive strategies discussed, including vaccination and antiviral therapy. The timing and severity of these infections are pivotal in determining their impact on fetal heart development. Environmental exposures and maternal nutrition are critical factors influencing fetal development. Maternal undernutrition in low- and middle-income countries associates with adverse pregnancy outcomes, including congenital heart defects. Emphasizing the importance of maintaining a nutritious maternal diet, rich in essential nutrients, is crucial for improved fetal health and successful pregnancy outcomes. This review offers insights into preventive measures and underscores the need for continued research to enhance prenatal care strategies

Exploring the pastiche hegemony of men

In this article I explore the continued hegemony of certain men. I use interview extracts to help think through the notion of pastiche hegemony as a means of understanding how men, and narratives about them, have changed, but unequal power relations persist. In particular, I explore this process within men’s understandings of how they were able to gain and maintain influence and power at work. Through their reflexive reading of the changing shape of late modern Western society, these men believed they were able to craft selves and employ social scripts to produce social influence and power in situational and contingent forms. I argue that it is within this interactional process that the increasingly undermined ideological and material legacy of patriarchy might still be reified. As such, while there is clear evidence highlighting the undermining of men’s ability to assume power, within this article I theoretically unpack how certain men might be able to produce a localized, pastiche hegemony. This article is published as part of a thematic collection on gender studies

Feeding Blueberry Diets in Early Life Prevent Senescence of Osteoblasts and Bone Loss in Ovariectomized Adult Female Rats

Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied.In this report, we show that feeding a high quality diet supplemented with blueberries (BB) to pre-pubertal rats throughout development or only between postnatal day 20 (PND20) and PND34 prevented ovariectomy (OVX)-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation.These results indicate: 1) a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2) the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence

Enhancing innovation between scientific and indigenous knowledge: pioneer NGOs in India

Abstract Background Until recently, little attention has been paid to local innovation capacity as well as management practices and institutions developed by communities and other local actors based on their traditional knowledge. This paper doesn't focus on the results of scientific research into innovation systems, but rather on how local communities, in a network of supportive partnerships, draw knowledge for others, combine it with their own knowledge and then innovate in their local practices. Innovation, as discussed in this article, is the capacity of local stakeholders to play an active role in innovative knowledge creation in order to enhance local health practices and further environmental conservation. In this article, the innovative processes through which this capacity is created and reinforced will be defined as a process of "ethnomedicine capacity". Methods The field study undertaken by the first author took place in India, in the State of Tamil Nadu, over a period of four months in 2007. The data was collected through individual interviews and focus groups and was complemented by participant observations. Results The research highlights the innovation capacity related to ethnomedical knowledge. As seen, the integration of local and scientific knowledge is crucial to ensure the practices anchor themselves in daily practices. The networks created are clearly instrumental to enhancing the innovation capacity that allows the creation, dissemination and utilization of 'traditional' knowledge. However, these networks have evolved in very different forms and have become entities that can fit into global networks. The ways in which the social capital is enhanced at the village and network levels are thus important to understand how traditional knowledge can be used as an instrument for development and innovation. Conclusion The case study analyzed highlights examples of innovation systems in a developmental context. They demonstrate that networks comprised of several actors from different levels can synergistically forge linkages between local knowledge and formal sciences and generate positive and negative impacts. The positive impact is the revitalization of perceived traditions while the negative impacts pertain to the transformation of these traditions into health commodities controlled by new elites, due to unequal power relations

Mutational Analysis of EGFR and Related Signaling Pathway Genes in Lung Adenocarcinomas Identifies a Novel Somatic Kinase Domain Mutation in FGFR4

BACKGROUND: Fifty percent of lung adenocarcinomas harbor somatic mutations in six genes that encode proteins in the EGFR signaling pathway, i.e., EGFR, HER2/ERBB2, HER4/ERBB4, PIK3CA, BRAF, and KRAS. We performed mutational profiling of a large cohort of lung adenocarcinomas to uncover other potential somatic mutations in genes of this signaling pathway that could contribute to lung tumorigenesis. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed genomic DNA from a total of 261 resected, clinically annotated non-small cell lung cancer (NSCLC) specimens. The coding sequences of 39 genes were screened for somatic mutations via high-throughput dideoxynucleotide sequencing of PCR-amplified gene products. Mutations were considered to be somatic only if they were found in an independent tumor-derived PCR product but not in matched normal tissue. Sequencing of 9MB of tumor sequence identified 239 putative genetic variants. We further examined 22 variants found in RAS family genes and 135 variants localized to exons encoding the kinase domain of respective proteins. We identified a total of 37 non-synonymous somatic mutations; 36 were found collectively in EGFR, KRAS, BRAF, and PIK3CA. One somatic mutation was a previously unreported mutation in the kinase domain (exon 16) of FGFR4 (Glu681Lys), identified in 1 of 158 tumors. The FGFR4 mutation is analogous to a reported tumor-specific somatic mutation in ERBB2 and is located in the same exon as a previously reported kinase domain mutation in FGFR4 (Pro712Thr) in a lung adenocarcinoma cell line. CONCLUSIONS/SIGNIFICANCE: This study is one of the first comprehensive mutational analyses of major genes in a specific signaling pathway in a sizeable cohort of lung adenocarcinomas. Our results suggest the majority of gain-of-function mutations within kinase genes in the EGFR signaling pathway have already been identified. Our findings also implicate FGFR4 in the pathogenesis of a subset of lung adenocarcinomas

Pregnane X Receptor and Yin Yang 1 Contribute to the Differential Tissue Expression and Induction of CYP3A5 and CYP3A4

The hepato-intestinal induction of the detoxifying enzymes CYP3A4 and CYP3A5 by the xenosensing pregnane X receptor (PXR) constitutes a key adaptive response to oral drugs and dietary xenobiotics. In contrast to CYP3A4, CYP3A5 is additionally expressed in several, mostly steroidogenic organs, which creates potential for induction-driven disturbances of the steroid homeostasis. Using cell lines and mice transgenic for a CYP3A5 promoter we demonstrate that the CYP3A5 expression in these organs is non-inducible and independent from PXR. Instead, it is enabled by the loss of a suppressing yin yang 1 (YY1)-binding site from the CYP3A5 promoter which occurred in haplorrhine primates. This YY1 site is conserved in CYP3A4, but its inhibitory effect can be offset by PXR acting on response elements such as XREM. Taken together, the loss of YY1 binding site from promoters of the CYP3A5 gene lineage during primate evolution may have enabled the utilization of CYP3A5 both in the adaptive hepato-intestinal response to xenobiotics and as a constitutively expressed gene in other organs. Our results thus constitute a first description of uncoupling induction from constitutive expression for a major detoxifying enzyme. They also suggest an explanation for the considerable tissue expression differences between CYP3A5 and CYP3A4