Determining Which Prosthetic to Use During Aortic Valve Replacement in Patients Aged Younger than 70 Years: A Systematic Review of the Literature.

BACKGROUND: The choice of bioprosthesis versus mechanical prosthesis in patients aged less than 70 years undergoing aortic valve replacement (AVR) remains controversial, with guidelines disparate in their recommendations. The objective of this study was to explore outcomes after AVR for various age ranges based on type of prosthesis. METHODS: A systematic review was undertaken according to the Preferred Reporting Instructions for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by using Medline (PubMed), Cochrane, Web of Science, Embase, and Scopus databases. Rates of long-term survival (primary outcome), reoperation, major bleeding, thromboembolism, stroke, structural valve deterioration, and endocarditis were compared between subjects receiving biologic and mechanical prostheses. Findings were grouped into patients aged <60 years, aged ≤65 years, and finally aged <70 years. RESULTS: A total of 19 studies met inclusion criteria. Seven evaluated patients aged <60 years, 4 of which found mechanical prosthesis patients to have higher long-term survival, whereas the remaining studies found no difference. Eight additional studies included patients aged 65 years or younger, and 9 studies included patients aged <70 years. The former found no difference in survival between prosthesis groups, whereas the latter favored mechanical prostheses in 3 studies. Bleeding, thromboembolism, and stroke were more prevalent in patients with a mechanical prosthesis, whereas reoperation was more common in those receiving a bioprosthesis. CONCLUSIONS: Published literature does not preclude the use of bioprostheses for AVR in younger patients. As new valves are developed, the use of bioprosthetic aortic valves in younger patients will likely continue to expand. Clinical trials are needed to provide surgeons with more accurate guidelines.

Postnatal neurodevelopmental expression and glutamate-dependent regulation of the ZNF804A rodent homologue.

The zinc finger protein ZNF804A rs1344706 variant is a replicated genome-wide significant risk variant for schizophrenia and bipolar disorder. While its association with altered brain structure and cognition in patients and healthy risk allele carriers is well documented, the characteristics and function of the gene in the brain remains poorly understood. Here, we used in situ hybridization to determine mRNA expression levels of the ZNF804A rodent homologue, Zfp804a, across multiple postnatal neurodevelopmental time points in the rat brain. We found changes in Zfp804a expression in the rat hippocampus, frontal cortex, and thalamus across postnatal neurodevelopment. Zfp804a mRNA peaked at postnatal day (P) 21 in hippocampal CA1 and DG regions and was highest in the lower cortical layers of frontal cortex at P1, possibly highlighting a role in developmental migration. Using immunofluorescence, we found that Zfp804a mRNA and ZFP804A co-localized with neurons and not astrocytes. In primary cultured cortical neurons, we found that Zfp804a expression was significantly increased when neurons were exposed to glutamate [20µM], but this increase was blocked by the N-methyl-d-aspartate receptor (NMDAR) antagonist MK-801. Expression of Comt, Pde4b, and Drd2, genes previously shown to be regulated by ZNF804A overexpression, was also significantly changed in an NMDA-dependent manner. Our results describe, for the first time, the unique postnatal neurodevelopmental expression of Zfp804a in the rodent brain and demonstrate that glutamate potentially plays an important role in the regulation of this psychiatric susceptibility gene. These are critical steps toward understanding the biological function of ZNF804A in the mammalian brain.

Physiology of functional and effective networks in epilepsy.

Epilepsy is a network phenomenon characterized by atypical activity during seizure both at the level of single neurons and neural populations. The etiology of epilepsy is not completely understood but a common theme among proposed mechanisms is abnormal synchronization between neuronal populations. Recent advances in novel imaging and recording technologies have enabled the inference of comprehensive maps of both the anatomical and physiological inter-relationships between brain regions. Clinical protocols established for diagnosis and treatment of epilepsy utilize both advanced neuroimaging techniques and neurophysiological data. These growing clinical datasets can be further exploited to better understand the complex connectivity patterns in the epileptic brain. In this article, we review results and insights gained from the growing body of research focused on epilepsy from a network perspective. In particular, we put an emphasis on two different notions of network connectivity: functional and effective; and studies investigating these notions in epilepsy are highlighted. We also discuss limitations and opportunities in data collection and analyses that will further our understanding of epileptic networks and the mechanisms of seizures.