Integrated analysis of the molecular pathogenesis of FDXR-associated disease.

The mitochondrial flavoprotein ferredoxin reductase (FDXR) is required for biogenesis of iron-sulfur clusters and for steroidogenesis. Iron-sulfur (Fe-S) clusters are ubiquitous cofactors essential to various cellular processes, and an increasing number of disorders are associated with disruptions in the synthesis of Fe-S clusters. Our previous studies have demonstrated that hypomorphic mutations in FDXR cause a novel mitochondriopathy and optic atrophy in humans and mice, attributed in part to reduced function of the electron transport chain (ETC) as well as elevated production of reactive oxygen species (ROS). Inflammation and peripheral neuropathy are also hallmarks of this disease. In this paper, we demonstrate that FDXR mutation leads to significant optic transport defects that are likely to underlie optic atrophy, a major clinical presentation in FDXR patients, as well as a neurodegenerative loss of cells in the central nervous system (CNS). Molecular analysis indicates that FDXR mutation also leads to mitochondrial iron overload and an associated depolarization of the mitochondrial membrane, further supporting the hypothesis that FDXR mutations cause neurodegeneration by affecting FDXR\u27s critical role in iron homeostasis

Maternal hormonal milieu influence on fetal brain development

An adverse maternal hormonal environment during pregnancy can be associated with abnormal brain growth. Subtle changes in fetal brain development have been observed even for maternal hormone levels within the currently accepted physiologic ranges. In this review, we provide an update of the research data on maternal hormonal impact on fetal neurodevelopment, giving particular emphasis to thyroid hormones and glucocorticoids. Thyroid hormones are required for normal brain development. Despite serum TSH appearing to be the most accurate indicator of thyroid function in pregnancy, maternal serum free T4 levels in the first trimester of pregnancy are the major determinant of postnatal psychomotor development. Even a transient period of maternal hypothyroxinemia at the beginning of neurogenesis can confer a higher risk of expressive language and nonverbal cognitive delays in offspring. Nevertheless, most recent clinical guidelines advocate for targeted high-risk case finding during first trimester of pregnancy despite universal thyroid function screening. Corticosteroids are determinant in suppressing cell proliferation and stimulating terminal differentiation, a fundamental switch for the maturation of fetal organs. Not surprisingly, intrauterine exposure to stress or high levels of glucocorticoids, endogenous or synthetic, has a molecular and structural impact on brain development and appears to impair cognition and increase anxiety and reactivity to stress. Limbic regions, such as hippocampus and amygdala, are particularly sensitive. Repeated doses of prenatal corticosteroids seem to have short-term benefits of less respiratory distress and fewer serious health problems in offspring. Nevertheless, neurodevelopmental growth in later childhood and adulthood needs further clarification. Future studies should address the relevance of monitoring the level of thyroid hormones and corticosteroids during pregnancy in the risk stratification for impaired postnatal neurodevelopment.This work was supported by the grant "Doutoramento em Medicina Jose de Mello Saude 2014" by Jose de Mello Saude to AM

Picture this:A review of research relating to narrative processing by moving image versus language

Reading fiction for pleasure is robustly correlated with improved cognitive attainment and other benefits. It is also in decline among young people in developed nations, in part because of competition from moving image fiction. We review existing research on the differences between reading or hearing verbal fiction and watching moving image fiction, as well as looking more broadly at research on image or text interactions and visual versus verbal processing. We conclude that verbal narrative generates more diverse responses than moving image narrative. We note that reading and viewing narrative are different tasks, with different cognitive loads. Viewing moving image narrative mostly involves visual processing with some working memory engagement, whereas reading narrative involves verbal processing, visual imagery, and personal memory (Xu et al., 2005). Attempts to compare the two by creating equivalent stimuli and task demands face a number of challenges. We discuss the difficulties of such comparative approaches. We then investigate the possibility of identifying lower level processing mechanisms that might distinguish cognition of the two media and propose internal scene construction and working memory as foci for future research. Although many of the sources we draw on concentrate on English-speaking participants in European or North American settings, we also cover material relating to speakers of Dutch, German, Hebrew, and Japanese in their respective countries, and studies of a remote Turkish mountain community

Minimally Invasive Quadriceps Tendon Harvest and Graft Preparation for All-Inside Anterior Cruciate Ligament Reconstruction

The quadriceps tendon is an infrequently used graft option for anterior cruciate ligament reconstruction despite favorable clinical results in the literature with low donor site morbidity. It is a versatile graft that can be harvested with bone or as a soft tissue graft alone. In addition, it can be used for anatomic, double-bundle, transtibial, and all-inside reconstructions. The unique characteristics of the quadriceps tendon allow for the ability to harvest a single-bundle large-diameter graft and minimize disruption of normal anatomy, which makes the quadriceps tendon an excellent choice for all-inside techniques. Recently developed minimally invasive harvest techniques described in this note allow for a reproducible predictable and efficient harvest through a small incision