Local and systemic factors associated with quantitative stiffness of carotid plaque.

PURPOSE: Plaque stiffness in carotid artery stenosis is a clinically important factor involved in the development of stroke and surgical complications. The purpose of this study was to clarify which local and systemic factors are associated with the quantitatively measured stiffness of plaque. METHODS: The subjects were 104 consecutive patients who underwent carotid endarterectomy at our institution. To measure quantitative stiffness of plaque, we used an industrial hard meter in the operating room within 1 h after removal of plaque. Local factors related to carotid plaque hardness were evaluated, including maximum intima-media thickness (max IMT), degree of stenosis using the European Carotid Surgery Trial (ECST), presence of ulceration or calcification, and echo brightness on preoperative carotid ultrasound. The degree of stenosis was also evaluated using the North American Symptomatic Carotid Endarterectomy Trial method in digital subtraction angiography. Age, sex, and presence or absence of hypertension, diabetes, and dyslipidemia (low-density lipoprotein cholesterol and triglyceride [TG] levels) served as systemic factors and were compared with the quantitative stiffness of carotid plaque. RESULTS: In multivariate analysis, ECST stenosis degree, calcification, and IMT max as local factors affected plaque stiffness. As a systemic factor, plaque stiffness was statistically significantly negatively correlated with TG values in multivariate analysis (p < 0.05). CONCLUSION: The quantitative stiffness of the plaque was negatively correlated with TG levels as a systemic factor in addition to local factors. This might suggest that reducing high TG levels is associated with plaque stabilization.

Relationship Between Quantitative Tumor Consistency and Pathological Factors in Intracranial Meningioma.

BACKGROUND: The consistency of intracranial meningiomas is an important clinical factor because it affects the success of surgical resection. This study aimed at identifying and quantitatively measuring pathological factors that contribute to the consistency of meningiomas. Furthermore, we investigated the relationship between these factors and preoperative neuroradiological imaging. METHODS: We analyzed 42 intracranial meningioma specimens, which had been removed at our institution between October 2012 and March 2018. Consistency was measured quantitatively after resection using an industrial stiffness meter. For pathological evaluation, we quantitatively measured the collagen-fiber content through binarization of images of Azan-Mallory-stained section. We assessed calcification and necrosis semi-quantitatively using images acquired of Hematoxylin and Eosin stained samples. The relationship between collagen-fiber content rate and imaging findings was examined. RESULTS: The content of collagen fibers significantly positively correlated with meningioma consistency (p < 0.0001). Collagen-fiber content was significantly higher in low- and iso-intensity regions compared with high-intensity regions on the magnetic resonance T2-weighted images (p = 0.0148 and p = 0.0394, respectively). Calcification and necrosis showed no correlation with tumor consistency. CONCLUSIONS: The quantitative hardness of intracranial meningiomas positively correlated with collagen-fiber content; thus, the amount of collagen fibers may be a factor that determines the hardness of intracranial meningiomas. Our results demonstrate that T2-weighted images reflect the collagen-fiber content and are useful for estimating tumor consistency preoperatively and non-invasively.

The genome-wide DNA methylation profiles among neurosurgery patients with and without post-operative delirium.

AIMS: There is no previous study demonstrating the differences of genome-wide DNA methylation (DNAm) profiles between patients with and without postoperative delirium (POD). We aimed to discover epigenetic (DNAm) markers that are associated with POD in blood obtained from patients before and after neurosurgery. METHODS: Pre- and post-surgical blood DNA samples from 37 patients, including 10 POD cases, were analyzed using the Illumina EPIC array genome-wide platform. We examined DNAm differences in blood from patients with and without POD. Enrichment analysis with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms were also conducted. RESULTS: When POD cases were tested for DNAm change before and after surgery, enrichment analyses showed many relevant signals with statistical significance in immune response related-pathways and inflammatory cytokine related-pathways such as "cellular response to cytokine stimulus", "regulation of immune system process", "regulation of cell activation", and "regulation of cytokine production". Furthermore, after excluding the potential effect of common factors related to surgery and anesthesia between POD cases and non-POD controls, the enrichment analyses showed significant signals such as "immune response" and "T cell activation", which are same pathways previously identified from an independent non-surgical inpatient cohort. CONCLUSIONS: Our first genome-wide DNAm investigation of POD showed promising signals related to immune response, inflammatory response and other relevant signals considered to be associated with delirium pathophysiology. Our data supports the hypothesis that epigenetics play an important role in the pathophysiological mechanism of delirium and suggest the potential usefulness of an epigenetics-based biomarker of POD.

Genome-wide DNA methylation analysis of post-operative delirium with brain, blood, saliva, and buccal samples from neurosurgery patients.

OBJECTIVE: No previous study demonstrates the difference in the genome-wide DNA methylation status of post-operative delirium (POD) using human brain tissue obtained from neurosurgery and multiple peripheral tissues such as blood, saliva, and buccal samples from the same individuals. We aimed to identify epigenetic marks of DNA methylation in the brain and peripheral tissues to elucidate the potential pathophysiological mechanism of POD. METHODS: The four tissue types (brain, blood, saliva, buccal) of DNA samples from up to 40 patients, including 11 POD cases, were analyzed using Illumina EPIC array. DNAm differences between patients with and without POD were examined. We also conducted enrichment analysis based on the top DNAm signals. RESULTS: The most different CpG site between control and POD was found at cg16526133 near the ADAMTS9 gene from the brain tissue(p = 8.66E-08). However, there are no CpG sites to reach the genome-wide significant level. The enrichment analysis based on the 1000 top hit CpG site (p < 0.05) on the four tissues showed several intriguing pathways. In the brain, there are pathways including "positive regulation of glial cell differentiation". Blood samples showed also pathways related to immune function. Besides, both saliva and the buccal sample showed pathways related to circadian rhythm, although these findings were not FDR significant. CONCLUSION: Enrichment analysis found several intriguing pathways related to potential delirium pathophysiology. Present data may further support the role of epigenetics, especially DNA methylation, in the molecular mechanisms of delirium pathogenesis.

Brain Diseases and Fall-Related Surgery in Older Persons.

BACKGROUND: It is known that age-related brain symptoms (gait difficulty and dementia) increase the likelihood of fall-related surgery. In contrast, it is not known which types of brain disease underlie such symptoms most. OBJECTIVE: The aim of this study was to correlate brain diseases with the types of surgeries performed at our hospital for patients who had fallen. METHODS: This was a retrospective study at a multifaculty university hospital in Japan, with a 12-month recruiting period, a follow-up period of 3.0 ± 2.5 weeks, and ≥1×/week visits. We assembled a neurogeriatric team to diagnose brain diseases with the use of brain imaging to the extent possible and correlated the diagnoses with types of fall-related surgery. RESULTS: Fall-related surgery was conducted by the orthopedics (OP) and neurosurgery (NS) faculties (total n = 124) at a ratio of about 2 to 1. The underlying brain diseases differed by faculty; for OP, surgery was most commonly performed in patients with a combination of white matter disease (WMD) and Alzheimer's disease (AD) (79%) followed by dementia with Lewy bodies. In contrast, for NS, the most common surgery was for patients with alcoholism (50%) followed by a combination of WMD and AD. CONCLUSION: Fall-related surgery was performed by the OP and NS faculties at a 2 to 1 ratio. The major underlying brain diseases were a combination of WMD and AD (79%) for OP and alcoholism (50%) for NS.

Voice handicap Index in Parkinson's patients: Subthalamic versus globus pallidus deep brain stimulation.

PURPOSE: Subthalamic nucleus (STN) and globus pallidus interna (GPI) are the two most common sites for deep brain stimulation (DBS) in people with Parkinson's disease (PWP). Voice impairments are a common symptom of Parkinson's disease and information about voice outcomes with DBS is limited. Most studies in speech-language pathology have focused on STN-DBS and few have examined the effects of GPI-DBS. This was an initial effort to examine the impact of DBS location on Vocal Handicap Index (VHI) scores, which assess the impact of a voice disorder on an individual. METHOD: Twenty-four gender-matched PWP (12 STN-DBS and 12 GPI-DBS) completed the VHI post-DBS implantation. Two-tailed independent samples t-tests were used to compare each VHI scale score (physical, functional, emotional, total) and patient factors between the two groups. RESULTS: No significant differences in total or subscale VHI scores were identified between the two DBS groups. A trend toward greater impairment in PWP with GPI-DBS was noted. An association between higher VHI scores and DBS settings was found. CONCLUSIONS: Studies directly comparing speech outcomes for different DBS targets are lacking. The current findings provide new insights concerning voice outcomes following DBS by adding to the limited literature directly comparing speech outcomes in multiple DBS targets. Limitations and directions for future research are discussed.

DNA methylation in the inflammatory genes after neurosurgery and diagnostic ability of post-operative delirium.

The pathophysiological mechanisms of postoperative delirium (POD) are still not clear, and no reliable biomarker is available to differentiate those with and without POD. Pre- and post-surgery blood from epilepsy subjects undergoing neurosurgery were collected. DNA methylation (DNAm) levels of the TNF gene, IL1B gene, and IL6 gene by the Illumina EPIC array method, and DNAm levels of the TNF gene by pyrosequencing, were analyzed. Blood from 37 subjects were analyzed by the EPIC array method, and blood from 27 subjects were analyzed by pyrosequencing. Several CpGs in the TNF gene in preoperative blood showed a negative correlation between their DNAm and age both in the POD group and in the non-POD group. However, these negative correlations were observed only in the POD group after neurosurgery. Neurosurgery significantly altered DNAm levels at 17 out of 24 CpG sites on the TNF gene, 8 out of 14 CpG sites on the IL1B gene, and 4 out of 14 CpG sites on the IL6 gene. Furthermore, it was found that the Inflammatory Methylation Index (IMI), which was based on the post-surgery DNAm levels at the selected five CpG sites, can be a potential detection tool for delirium with moderate accuracy; area under the curve (AUC) value was 0.84. The moderate accuracy of this IMI was replicated using another cohort from our previous study, in which the AUC was 0.79. Our findings provide further evidence of the potential role of epigenetics and inflammation in the pathophysiology of delirium.

[Infected subdural hematoma having a surgery of chronic subdural hematoma 1 year ago:a case report].

We report a case of an infected subdural hematoma that occurred 1 year after burr-hole irrigation for chronic subdural hematoma. A 78-year-old woman who had developed left hemiparesis was admitted to our hospital. A computed tomography(CT)scan revealed the presence of a chronic subdural hematoma in the right hemisphere. Her clinical symptoms improved immediately after emergency burr-hole irrigation, which allowed her discharge from the hospital. One year after the initial surgery, she developed an infection of the urinary tract infection, which led to severe pyelonephritis and septic shock. Treatment of the urological symptoms eliminated the systemic inflammation. One month after the urinary infection, the patient was readmitted to the hospital in a comatose state. A CT scan showed regrowth of a residual subdural hematoma surrounded by a thick capsule, causing a midline shift in the brain. An emergency operation for removal of the subdural hematoma by burr-hole irrigation was performed, and pus was drained from the subdural mass. Microbiological cultures of the abscess revealed the presence of Proteus mirabilis. After surgery, the patient was administered an antibiotic treatment for three weeks and she was discharged with no neurological deficits. Cultures of blood from the septic shock as well as from the abscess both revealed the presence of Proteus mirabilis. Therefore, a diagnosis of infected subdural hematoma, which was caused by hematogenous infection, was made. We conclude that attention should be paid to the risk of infection of the hematoma capsule in subdural hematomas.

RSC Nucleosome-remodeling complex plays prominent roles in transcriptional regulation throughout budding yeast gametogenesis.

RSC is a nucleosome-remodeling complex of Saccharomyces cerevisiae essential for growth that can alter histone-DNA interaction by using the energy of ATP hydrolysis. Nps1p/Sth1p is an ATPase subunit of RSC. A mutation in the conserved ATPase domain of Nps1p causes a sporulation defect with decreased expression of early meiotic genes, especially IME2. This defect is partially suppressed by the overexpression of either IME1 or IME2. A homozygous diploid of a novel temperature-sensitive nps1 mutation, nps1-13, harboring amino acid substitutions within the bromodomain, was unable to sporulate. Overexpression of IME, IME2, or both of these genes allowed the completion of meiosis I and meiosis II in nps1-13 but not the formation of mature asci. In nps1-13 carrying YEpIME1, the expression of a group of sporulation-specific genes, which express at the middle stages of sporulation and are required for spore-wall formation, notably diminished, and several late sporulation genes expressed at the early stages of sporulation. These results suggest that Nps1p/RSC plays important roles during the spore development process by controlling gene expression for initiating both meiosis and spore morphogenesis, and ensures proper expression timing of late meiotic genes.