Deciphering the vascular labyrinth: role of microRNAs and candidate gene SNPs in brain AVM development - literature review.

Background: Brain arteriovenous malformations (AVMs) are a relatively infrequent vascular pathology of unknown etiology that, despite their rarity, cause the highest number of hemorrhagic strokes under the age of 30 years. They pose a challenge to all forms of treatment due to their variable morphology, location, size, and, last but not least, evolving nature. MicroRNAs (miRNAs) are non-coding RNA strands that may suppress the expression of target genes by binding completely or partially to their complementary sequences. Single nucleotide polymorphisms (SNPs), as the name implies, are variations in a single nucleotide in the DNA, usually found in the non-coding segments. Although the majority of SNPs are harmless, some located in the proximity of candidate genes may result in altered expression or function of these genes and cause diseases or affect how different pathologies react to treatment. The roles miRNAs and certain SNPs play in the development and growth of AVMs are currently uncertain, yet progress in deciphering the minutiae of this pathology is already visible. Methods and Results: We performed an electronic Medline (PubMed, PubMed Central) and Google Academic exploration using permutations of the terms: "arteriovenous malformations," "single nucleotide polymorphisms," "microRNA," "non-coding RNA," and "genetic mutations." The findings were then divided into two categories, namely the miRNAs and the candidate gene SNPs associated with AVMs respectively. 6 miRNAs and 12 candidate gene SNPs were identified and discussed. Conclusions: The following literature review focuses on the discoveries made in ascertaining the different implications of miRNAs and candidate gene SNPs in the formation and evolution of brain AVMs, as well as highlighting the possible directions of future research and biological treatment. Abbreviations: ACVRL1/ALK1: activin receptor-like kinase 1; Akt: protein kinase B; ANGPTL4: angiopoietin-like 4; ANRIL: antisense noncoding RNA in the INK4 locus; AVM: arteriovenous malformation; AVM-BEC: arteriovenous malformation brain endothelial cell; BRCA1: breast cancer type 1 susceptibility protein; CCS: case-control study; CDKN2A/B: cyclin-dependent kinase inhibitor 2A/B; CLTC: clathrin heavy chain; DNA: deoxyribonucleic acid; ERK: extracellular signal-regulated kinase; GPR124: probable G-protein coupled receptor 124; GWAS: genome-wide association study; HHT: hereditary hemorrhagic telangiectasia; HIF1A: hypoxia-inducible factor 1A; IA: intracranial aneurysm; ICH: intracranial hemorrhage; Id-1: inhibitor of DNA-binding protein A; IL-17: interleukin 17; MAP4K3: mitogen-activated protein kinase kinase kinase kinase 3; miRNA: microRNA; MMP: matrix metalloproteinase; NFkB: nuclear factor kappa-light-chain of activated B cells; NOTCH: neurogenic locus notch homolog; p38MAPK: p38 mitogen-activated protein kinase; PI3K: phosphoinositide 3-kinase; RBBP8: retinoblastoma-binding protein 8; RNA: ribonucleic acid; SNAI1: Snail Family Transcriptional Repressor 1; SNP: single nucleotide polymorphism; SOX-17: SRY-related HMG-box; TGF-ß: transformation growth factor ß; TGFR: transformation growth factor receptor; TIMP-4, tissue inhibitor of metalloproteinase 4; TSP-1: thrombospondin-1; UTR: untranslated region; VEGF: Vascular Endothelial Growth Factor; VSMC: vascular smooth muscle cell; Wnt1: Wnt family member 1.

Gender Differences in the Self-assessment of Quality of Life and Disability After Spinal Fusion for Chronic Low Back Pain at a Neurosurgical Center in Eastern Europe.

OBJECTIVE: Mechanical alterations of the spine, which can cause chronic low back pain (LBP), are a frequent indication for spinal fusion. Studies have shown differences between genders in patients' evaluations of health-related quality of life (HRQoL) after spinal procedures, but results have been conflicting, and some authors have suggested that cultural variation could explain these discrepancies. The objectives of this study were to determine the influence that gender plays on HRQoL, disability, and the correlation between the 2 in people undergoing spinal fusion for chronic LBP at a neurosurgical centre in Eastern Europe. METHODS: Patients undergoing fusion surgery at a single centre for LBP with a duration of more than 3 months were included. They were evaluated using the Short Form Health Survey version-2.0 (SF-36v2) and Oswestry Low Back Pain Disability Index (ODI) questionnaire preoperatively and 1 year after the surgical procedure to identify differences between genders and to evaluate correlations between disability and quality of life. RESULTS: We included 31 female and 30 male patients. The male patients had higher disability scores at the preoperative evaluation, but improved more than females in all domains of disability at the postoperative evaluation. HRQoL improved similarly in both genders. The ODI score showed a strong or moderate correlation with 6 of the domains of the SF-36 in males, but with only 3 domains in females. Surgery had a positive impact on the mental status of more men than women at risk of depression. CONCLUSION: The type of benefit that surgery offers seems to be influenced by gender. While HRQoL improved in both genders, disability decreased significantly more in male patients. Male patients also showed a closer correlation between HRQoL and disability. We conclude that men and women place different importance on specific aspects of their overall quality of life.

Influence of Gender on Health-Related Quality of Life and Disability at 1 Year After Surgery for Thoracolumbar Burst Fractures.

STUDY DESIGN: Case series. OBJECTIVE: Thoracolumbar burst fractures (TLBF) are the most frequent type of spinal fractures. Approximately half of the patients are neurologically intact and their treatment is still debatable. Gender could influence outcome after surgical procedures, but this is still unclear in patients sustaining a spinal fracture. The aim of this study was to investigate how gender influences health-related quality of life (HRQOL) and disability in patients operated on for TLBF. METHODS: We identified 44 neurologically intact patients from a consecutive series of patients treated surgically for a single-level traumatic burst fracture (AOSpine Subaxial Classification System A3) in the thoracolumbar transition area (Th12-L2). At 1 year after surgery, they were evaluated using the SF-36v2 questionnaire to assess HRQOL and Oswestry Disability Index (ODI) questionnaire to evaluate disability. RESULTS: Male patients scored higher in each item of the SF-36v2, with significant differences (P < .05) for Physical Function (PF), Bodily Pain (BP), and Social Function (SF). Male patients also had lower disability scores. Overall ODI score had a strong correlation with Physical Function, Role-Physical, Bodily Pain, Vitality, Mental Health, and overall Physical Component Summary (PCS) of the SF-36 in women, but only with Physical Function, Role-Physical, Role-Emotional, and PCS in men. CONCLUSIONS: In this study, male patients reported better outcomes at 1 year after surgery for TLBF than women. Disability strongly correlated with the overall HRQOL, physical and mental health in women, but not in men. We found gender-related differences favoring men after surgical interventions for spinal fractures.

Cutaneous wound healing using polymeric surgical dressings based on chitosan, sodium hyaluronate and resveratrol. A preclinical experimental study.

Wound healing is a complex and dynamic process that involves modifying the wound environment depending on the patient's health status. Scar formation depends on many factors that influence wound healing, are important to bear in mind because most of the negative factors involved can be stopped by implementing an adequate treatment. The consensus in wound therapy recommends dressings that should keep a moist and alkaline environment thus creating a protective barrier against mechanical stress and secondary infections, in view of promoting granulation. In the current paper, we aimed to synthesize a polymer-based sponge containing chitosan-sodium hyaluronate-resveratrol (CHR) and to evaluate its regenerative potential. The process of synthesizing the CHR polymer was described before microtomography analysis was conducted and the density and porosity of the obtained sponges was assessed. The cytotoxicity was evaluated in vitro. By undertaking the in vivo testing of the CHR polymer, we aimed to determine the CHR sponge's potential to stimulate tissue regeneration after inflicting a controlled, reproducible and measurable skin wound in an animal model. Skin punch biopsies were harvested from the healed area and were subjected to histopathological evaluation. The results obtained in this study confirmed that this polymer accelerates the formation of granulation facilitating wound healing, while also achieving a bacteriostatic outcome.

Health-related quality of life in patients undergoing lumbar total disc replacement: A comparison with the general population.

OBJECTIVES: In up to half of the cases, low back pain (LBP) is thought to be related to a degeneration of the lumbar disc. Lumbar total disc replacement (LTDR) emerged as an alternative to fusion, but its use and indications are still subject to debate. The purpose of this paper was to compare Health-related Quality of life (HRQOL) in patients undergoing LTDR for one or two-level degenerative disc disease (DDD) with the paired age and gender general population values and to assess functional disability and residual pain at one year after the surgical procedure. MATERIAL AND METHODS: A series of 51 patients operated on for a one or two level DDD, were evaluated at one year after the surgical procedure. HRQOL was compared to that of paired age and gender general population using the EQ-5D-5L questionnaire. Disability, back (BP) and leg pain (LP) were compared to the preoperative values. RESULTS: ODI showed a mean improvement of 31.78 (p<0.001, 95% CI 27.39-36.17), BP-VAS of 5.29/10 (95% CI 4.56-6.02), LP-VAS of 4.03/10 (95% CI 3.15-4.92) at one year compared to the preoperative assessment. HRQOL had similar values to the general population in 32 patients and inferior in 19 patients. "Pain" was the HRQOL dimension in which most of the patients had inferior results compared to data from the general population. Patients with previous spinal surgery had lower improvements in HRQOL index, disability, and pain than those without previous surgery. CONCLUSIONS: We found that the majority of patients improved their HQOL to values similar to those of the general population. Disability and pain are significantly reduced compared to preoperative evaluations. Larger scale studies are needed to identify the best candidates for LTDR.

Fluorescein Angiography in Intracranial Aneurysm Surgery: A Helpful Method to Evaluate the Security of Clipping and Observe Blood Flow.

BACKGROUND: In cerebral aneurysm surgery, various tools are used to evaluate blood flow, including Doppler ultrasonography, conventional cerebral angiography, and electrophysiological monitoring. Fluorescein and indocyanine green are widely used in vascular and central nervous system tumor neurosurgery; however, their routine utilization in aneurysmal surgery is uncommon, despite the fact that they allow direct visualization of blood flow after aneurysmal sac occlusion, enabling the observation of vessel permeability and the effectiveness of aneurysmal obliteration. We report our initial experience using fluorescein video angiography as a control measure for proper clip placement and control of blood flow in aneurysm surgery, and review the relevant literature. METHODS: This pilot study presents an initial experience, with enrollment of 10 patients harboring a total of 12 cerebral aneurysms who underwent surgery via clipping and subsequent fluorescence videoangiography control. The intravenous injection was performed to demonstrate the patency of the arteries adjacent to the aneurysm. RESULTS: Following intravenous injection, fluorescein sodium remains in the cerebral vasculature for approximately 3 minutes, providing ample time to evaluate vessel patency and determine whether clip repositioning is needed. None of the patients experienced complications during intravenous injection of fluorescein sodium, and the patency of surrounding vessels was demonstrated in all cases. CONCLUSIONS: Fluorescein injection in itself does not present a risk of complications, is simple to use, and offers a clear image of the cerebral vasculature. Thus, this technique is useful for determining vessel patency and the degree of aneurysmal occlusion.