Differential DNA methylation associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a systematic review.

Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.

Gut microbiome in intracranial aneurysm growth, subarachnoid hemorrhage, and cerebral vasospasm: a systematic review with a narrative synthesis.

Intracranial aneurysms (IA) are the most common cerebral vascular pathologies. Their rupture leads to the most dangerous subtype of stroke-aneurysmal subarachnoid hemorrhage (aSAH), which may be followed by cerebral vasospasm and ischemic sequelae. Recently, an imbalance within the intestinal microbiota, referred to as dysbiosis, was suggested to play a role in the formation, progression, and rupture of IA. As no systematic review on this topic exists, considering the significance of this matter and a lack of effective prophylaxis against IA or cerebral vasospasm, we aim to sum up the current knowledge regarding their associations with intestinal microbiome, identify the gaps, and determine future prospects. Scientific databases were systematically and independently searched by two authors from inception to 1st May 2023 for original articles regarding the role of intestinal microbiota in intracranial aneurysmal growth, aSAH occurrence, as well as in cerebral vasospasm following aSAH. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist was followed in an abstraction process. The STROBE tool was applied to assess the risk of bias. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 302 records, four studies were included that fully met eligibility criteria. Studies reported (1) that the relative abundance of Hungatella hathewayi is a protective factor against aneurysm growth and rupture, resulting from the reduced inflammation and extracellular matrix remodeling in the cerebral arterial wall and from reduced metalloproteinase-mediated degradation of smooth muscle cells in cerebral vessels. (2) Relative abundance of Campylobacter ureolyticus is associated with aSAH. (3) No article has evaluated microbiota in relation to cerebral vasospasm following aSAH although there is an ongoing study. We concluded that intestinal microbiota might be a potential target for diagnostic and therapeutic tools to improve the management of cerebral aneurysms. However, more studies of prospective design are needed.

The Role of Adipokines in the Pathogenesis of Psoriasis.

Psoriasis is a chronic and immune-mediated skin condition characterized by pro-inflammatory cytokines and keratinocyte hyperproliferation. Dendritic cells, T lymphocytes, and keratinocytes represent the main cell subtypes involved in the pathogenesis of psoriasis, while the interleukin-23 (IL-23)/IL-17 pathway enhances the disease progression. Human adipose tissue is an endocrine organ, which secretes multiple proteins, known as adipokines, such as adiponectin, leptin, visfatin, or resistin. Current evidence highlights the immunomodulatory roles of adipokines, which may contribute to the progression or suppression of psoriasis. A better understanding of the complexity of psoriasis pathophysiology linked with adipokines could result in developing novel diagnostic or therapeutic strategies. This review aims to present the pathogenesis of psoriasis and the roles of adipokines in this process.

Latest models for the discovery and development of rheumatoid arthritis drugs.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease that reduces the quality of life. The current speed of development of therapeutic agents against RA is not satisfactory. Models on which initial experiments are conducted do not fully reflect human pathogenesis. Overcoming this oversimplification might be a crucial step to accelerate studies on RA treatment. AREAS COVERED: The current approaches to produce novel models or to improve currently available models for the development of RA drugs have been discussed. Advantages and drawbacks of two- and three-dimensional cell cultures and animal models have been described based on recently published results of the studies. Moreover, approaches such as tissue engineering or organ-on-a-chip have been reviewed. EXPERT OPINION: The cell cultures and animal models used to date appear to be of limited value due to the complexity of the processes involved in RA. Current models in RA research should take into account the heterogeneity of patients in terms of disease subtypes, course, and activity. Several advanced models and tools using human cells and tissues have been developed, including three-dimensional tissues, liquid bioreactors, and more complex joint-on-a-chip devices. This may increase knowledge of the molecular mechanisms leading to disease development, to help identify new biomarkers for early detection, and to develop preventive strategies and more effective treatments.

Searching for the Mechanism of Action of Extremely Low Frequency Electromagnetic Field-The Pilot fNIRS Research.

There is an ongoing debate on the benefits of magnetic stimulation in neurological disorders. OBJECTIVES: We aimed to evaluate the influence of magnetic stimulation on blood oxygenation of the motor cortex using functional near-infrared spectroscopy (fNIRS). METHODS: A total of 16 healthy volunteer participants were subjected to four protocols. In the first two protocols, the participants remained at rest without (and then with) magnetic stimulation. In the next two protocols, motor cortex stimulation was achieved using a finger-tapping task, with and without magnetic stimulation. Changes in blood oxygenation levels within the motor cortex were recorded and analysed. RESULTS: No characteristic changes in the blood oxygenation level-dependent responses were observed in resting participants after magnetic stimulation. No statistically significant difference was observed in the amplitude of the fNIRS signal before and after magnetic stimulation. We observed characteristic blood oxygenation level-dependent responses after the finger-tapping task in the second protocol, but not after magnetic stimulation. CONCLUSIONS: Although we did not observe any measurable effect of the magnetic field on the haemodynamic response of the motor cortex, understanding the mechanism(s) of magnetic stimulation may be important. Additional, detailed studies are needed to prove or negate the potential of this medical procedure.

Prevalence of high-riding vertebral arteries and narrow C2 pedicles among Central-European population: a computed tomography-based study.

High-riding vertebral artery (HRVA) and narrow C2 pedicles (C2P) pose a great risk of injuring the vessel during C2 pedicle or transarticular screw placement. Recent meta-analysis revealed a paucity of European studies regarding measurements and prevalence of these anatomical variants. Three hundred eighty-three consecutive cervical spine CT scans with 766 potential screw insertion sites were analyzed independently by two trained observers. C2 internal height (C2InH), C2 isthmus height (C2IsH), and C2P width were measured. Kappa statistics for inter- and intraobserver reliability as well as for inter-software agreement were calculated. HRVA was defined as C2IsH of ≤ 5 mm and/or C2InH of ≤ 2 mm. Narrow C2P was defined as C2P width ≤ 4 mm. STROBE checklist was followed. At least 1 HRVA was found in 25,3% (95% CI 21,1-29,8) of patients (16,7% of potential sites). At least 1 narrow C2P was seen in 36,8% (95% CI 32,1-41,7) of patients (23,8% of potential sites). Among those with HRVA, unilateral HRVA was present in 68,0% (95% CI 58,4-77,0), whereas bilateral HRVA in 32,0% (95% CI 23,0-41,6). No difference in terms of laterality (right or left) was seen neither for HRVA nor narrow C2P. Significant differences were found between females and males for all measurements. Each parameter showed either good or excellent inter- or intraobserver, and inter-software agreement coefficients. HRVA and narrow C2P are common findings in Central-European population and should be appreciated at the planning stage before craniocervical instrumentation. Measurements can be consistently reproduced by various observers at varying intervals using different software.

Prevalence of High-Riding Vertebral Artery: A Meta-Analysis of the Anatomical Variant Affecting Choice of Craniocervical Fusion Method and Its Outcome.

OBJECTIVE: A high-riding vertebral artery (HRVA) has been defined as a C2 isthmus height of ≤5 mm and/or internal height of ≤2 mm measured 3 mm lateral to the border of the spinal canal. Its reported prevalence has varied widely. If overlooked during the approach for craniocervical fusion, injury to the vertebral arteries can occur, affecting the outcome. The present meta-analysis aimed to provide the pooled prevalence of HRVAs. METHODS: A comprehensive database search was conducted by 3 of us. Peer-reviewed studies that had followed the strict definition for HRVAs and had reported its prevalence were included. The risk of bias was assessed using the anatomical quality assessment tool. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. The pooled prevalence was calculated using a random effects model. RESULTS: The data from 20 studies with 3126 subjects (7496 sides) were analyzed. The overall pooled prevalence of ≥1 HRVA was 25.3% (95% confidence interval [CI], 19.6%-31.5%). The prevalence in those without the most important confounding factor, rheumatoid arthritis (RA), was 20.9% (95% CI, 16.5%-25.8%). Patients with RA had a prevalence of 42.9% (95% CI, 23.8%-63.1%). The difference between the non-RA and RA groups was statistically significant (P < 0.001, test of homogeneity, χ2). No geographical differences were noted (P = 0.20, test of homogeneity, χ2). Among those with HRVA, unilateral HRVA was present in 70.3% (95% CI, 65.2%-75.2%) and bilateral in 29.7% (95% CI, 24.8%-34.8%). No left or right side predilection was found (left, 50.8%; 95% CI, 33.8%-67.6%; right, 49.2%; 95% CI, 32.4%-66.2%). CONCLUSIONS: Craniocervical fusion should be preceded by examination of the vertebral arteries at the level of C2 because the presence of HRVAs is common and might preclude the safe insertion of transarticular or transpedicular screws.