Biomechanical Analysis of Age-Dependent Changes in Fontan Power Loss.

The hemodynamics in Fontan patients with single ventricles rely on favorable flow and energetics, especially in the absence of a subpulmonary ventricle. Age-related changes in energetics for extracardiac and lateral tunnel Fontan procedures are not well understood. Vorticity (VOR) and viscous dissipation rate (VDR) are two descriptors that can provide insights into flow dynamics and dissipative areas in Fontan pathways, potentially contributing to power loss. This study examined power loss and its correlation with spatio-temporal flow descriptors (vorticity and VDR). Data from 414 Fontan patients were used to establish a relationship between the superior vena cava (SVC) to inferior vena cava (IVC) flow ratio and age. Computational flow modeling was conducted for both extracardiac conduits (ECC, n = 16) and lateral tunnels (LT, n = 25) at different caval inflow ratios of 2, 1, and 0.5 that corresponded with ages 3, 8, and 15+. In both cohorts, vorticity and VDR correlated well with PL, but ECC cohort exhibited a slightly stronger correlation for PL-VOR (>0.83) and PL-VDR (>0.89) than that for LT cohort (>0.76 and > 0.77, respectively) at all ages. Our data also suggested that absolute and indexed PL increase (p < 0.02) non-linearly as caval inflow changes with age and are highly patient-specific. Comparison of indexed power loss between our ECC and LT cohort showed that while ECC had a slightly higher median PL for all 3 caval inflow ratio examined (3.3, 8.3, 15.3) as opposed to (2.7, 7.6, 14.8), these differences were statistically non-significant. Lastly, there was a consistent rise in pressure gradient across the TCPC with age-related increase in IVC flows for both ECC and LT Fontan patient cohort. Our study provided hemodynamic insights into Fontan energetics and how they are impacted by age-dependent change in caval inflow. This workflow may help assess the long-term sustainability of the Fontan circulation and inform the design of more efficient Fontan conduits.

Impact of Age-related change in Caval Flow Ratio on Hepatic Flow Distribution in Fontan.

Background: The Fontan operation is a palliative technique for patients born with single ventricle heart disease. The superior vena cava (SVC), inferior vena cava (IVC), and hepatic veins are connected to the pulmonary arteries in a total cavopulmonary connection by an extracardiac (EC) conduit or a lateral tunnel (LT) connection. A balanced hepatic flow distribution (HFD) to both lungs is essential to prevent pulmonary arteriovenous malformations and cyanosis. HFD is highly dependent on the local hemodynamics. Objective: The effect of age-related changes in caval inflows on HFD was evaluated using cardiac MRI (CMR) data and patient-specific computational fluid dynamics (CFD) modeling. Methods: SVC and IVC flow from 414 Fontan patients were collected to establish a relationship between SVC:IVC flow ratio and age. CFD modeling was performed in 60 (30 EC and 30 LT) patient models to quantify the HFD that corresponded to patient ages of 3, 8, and 15 years, respectively. Results: SVC:IVC flow ratio inverted at ∼8 years of age, indicating a clear shift to lower body flow predominance. Our data showed that variation of HFD in response to age-related changes in caval inflows (SVC:IVC = 2,1, and 0.5 corresponded to ages 3, 8, and 15+ respectively) was not significant for EC but statistically significant for LT cohorts. For all three caval inflow ratios, a positive correlation existed between the IVC flow distribution to both the lungs and the HFD. However, as the SVC:IVC ratio changed from 2→0.5 (age 3→15+), the correlation's strength decreased from 0.87→0.64, due to potential flow perturbation as IVC flow momentum increased. Conclusion: Our analysis provided quantitative insights into the impact of the changing caval inflows on Fontan's long-term HFD, highlighting the importance of including SVC:IVC variations over time to understand Fontan's long-term hemodynamics. These findings broaden our understanding of Fontan hemodynamics and patient outcomes. Clinical Perspective: With improvement in standard of care and management of single ventricle patients with Fontan physiology, the population of adults with Fontan circulation is increasing. Consequently, there is a clinical need to comprehend the impact of patient growth on Fontan hemodynamics. Using CMR data, we were able to quantify the relationship between changing caval inflows and somatic growth. We then used patient-specific computational flow modeling to quantify how this relationship affected the distribution of long-term hepatic flow in extracardiac and lateral tunnel Fontan types. Our findings demonstrated the significance of including SVC:IVC changes over time in CFD modeling to learn more about the long-term hemodynamics of Fontan. Fontan surgical approaches are increasingly planned and optimized using computational flow modeling. For a patient undergoing a Fontan procedure, the workflow presented in this study that takes into account the variations in Caval inflows over time can aid in predicting the long-term hemodynamics in a planned Fontan pathway.

From development to disease: diverse functions of NMDA-type glutamate receptors in the lower auditory pathway.

N-methyl-D-aspartate receptors (NMDA-Rs) are located at each synapse in the lower auditory pathway of mammals and avians. Characterized by a slow and long-lasting excitatory response upon glutamate activation, their existence in a sensory system biologically engineered for speed and precision seems counterintuitive. In this review we consider the diverse functions of NMDA-Rs. Their developmental regulation and unique subunit composition in the inner ear promote protective and neurotrophic roles following acute insult by regulating AMPA-R expression and assisting in the restoration of synaptic inputs. This contrasts with chronic damage where overactivation of NMDA-Rs is implicated in neuronal death. These functions are thought to be involved in auditory diseases, including noise-induced hearing loss, neural presbycusis, and tinnitus via aberrant excitation. A more traditional role emerges in the developing auditory brainstem, where NMDA-Rs are downregulated and switch subunit composition with maturation. Their biophysical properties also contribute to synaptic dynamics resembling long-term plasticity. At mature synapses they support reliable auditory processing by increasing the probability of action potential generation, regulating first-spike latency, and maintaining reliable action potential firing. Thus, NMDA-R functions in the lower auditory pathway are diverse, contributing to synaptic development, plasticity, temporal processing, and diseases.

Social perception in people with eating disorders.

OBJECTIVE: Social perception is a key aspect of social cognition which has so far not been investigated in eating disorders (ED). This study aimed to investigate social perception in individuals with anorexia nervosa (AN) and bulimia nervosa (BN). METHODS: Outpatients with AN (restricting subtype [AN-R]: n=51; binge-purge subtype [AN-BP]: n=26) or BN (n=57) and 50 healthy control (HC) participants completed the Interpersonal Perception Task (IPT-15). This is an ecologically valid task, which consists of 15 video clips, depicting complex social situations relating to intimacy, status, kinship, competition and deception. The participants have to assess relationships between protagonists' based on non-verbal cues. RESULTS: Overall, there was no difference between groups on the IPT total score and subscale scores. Group differences on the Intimacy subscale approached significance so post hoc comparisons were carried out. HCs performed significantly better than AN-R participants in determining the degree of intimacy between others. CONCLUSIONS: Social perception is largely preserved in ED patients. Individuals with AN-R show impairments in identifying intimacy in social situations, this may be due to the lack of relationship experience. Further research into different aspects of social cognition is required to establish the link between interpersonal difficulties and ED psychopathology.

TETRASPORE encodes a kinesin required for male meiotic cytokinesis in Arabidopsis.

A key step in pollen formation is the segregation of the products of male meiosis into a tetrad of microspores, each of which develops into a pollen grain. Separation of microspores does not occur in tetraspore (tes) mutants of Arabidopsis thaliana, owing to the failure of male meiotic cytokinesis. tes mutants thus generate large 'tetraspores' containing all the products of a single meiosis. Here, we report the positional cloning of the TES locus and details of the role played by the TES product in male cytokinesis. The predicted TES protein includes an N-terminal domain homologous to kinesin motors and a C-terminus with little similarity to other proteins except for a small number of plant kinesins. These include the Arabidopsis HINKEL protein and NACK1 and two from tobacco (Nishihama et al., 2002), which are involved in microtubule organization during mitotic cytokinesis. Immunocytochemistry shows that the characteristic radial arrays of microtubules associated with male meiotic cytokinesis fail to form in tes mutants. The TES protein therefore is likely to function as a microtubule-associated motor, playing a part either in the formation of the radial arrays that establish spore domains following meiosis, or in maintaining their stability.

Early agalactosylation of IgG is associated with a more progressive disease course in patients with rheumatoid arthritis: results of a follow-up study.

The clinical significance of the percentage agalactosyl IgG oligosaccharides [%G(O)] was investigated in serum of a well-characterized cohort of 127 female RA patients who were followed for a mean duration of 6 yr. The %G(O) was determined in the first available serum sample which was obtained at a mean of 3.4 yr after symptom onset. It could be shown that patients with a %G(O) more than 2 S.D. above the mean level of controls (n = 34), had significantly more erosions, disease activity, and were treated with more second-line drugs, than patients without an increased %G(O) (n = 93), both at the time the serum sample was obtained, and during follow-up. These findings suggest that G(O) may serve as an indicator for the disease course in patients with RA.

Secretion of the Rhizobium leguminosarum nodulation protein NodO by haemolysin-type systems.

The Rhizobium leguminosarum biovar viciae nodulation protein NodO is partially homologous to haemolysin of Escherichia coli and, like haemolysin, is secreted into the growth medium. The NodO protein can be secreted by a strain of E. coli carrying the cloned nodO gene plus the haemolysin secretion genes hlyBD, in a process that also requires the outer membrane protein encoded by tolC. The related protease secretion genes, prtDEF, from Erwinia chrysanthemi also enable E. coli to secrete NodO. The Rhizobium genes encoding the proteins required for NodO secretion are unlinked to nodO and are unlike other nod genes, since they do not require flavonoids or NodO for their expression. Although proteins similar to NodO were not found in rhizobia other than R. leguminosarum bv. viciae, several rhizobia and an Agrobacterium strain containing the cloned nodO gene were found to have the ability to secrete NodO. These observations indicate that a wide range of the Rhizobiaceae have a protein secretion mechanism analogous to that which secretes haemolysin and related toxins and proteases in the ENterobacteriaceae.