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Neuropsychiatric Disease and Treatment 2022To explore the disease manifestations and radiological characteristics of patients with meningeal carcinomatosis (MC) combined with myelopathy.
OBJECTIVE
To explore the disease manifestations and radiological characteristics of patients with meningeal carcinomatosis (MC) combined with myelopathy.
PATIENTS AND METHODS
The detailed medical information of patients who suffered from MC with myelopathy in record system were collected and reviewed.
RESULTS
In these patients, five cases were male and two cases were female. The age was from fifteen to fifty-seven years. In the course of disease, tumor cells were discovered in cerebrospinal fluid of three patients and in biopsy samples of four patients. Cerebrospinal fluid (CSF) test results showed white blood cell counts increased in seven patients, protein increased in six patients and glucose reduced in five patients. In addition, MRI revealed that the white matter abnormalities showed in all cases and pia mater was enhanced in four patients, meningeal enhanced was observed in three patients. All patients were given appropriate therapy during hospitalization. Follow-up result showed that all patients passed away two to five months after diagnosis.
CONCLUSION
MC causes spinal membrane, spinal nerve root to be involved besides, also can produce the matter of myelopathy. Early detection of intramedullary lesion is conducive to strengthening the awareness of the diagnosis of MC.
PubMed: 35615422
DOI: 10.2147/NDT.S329180 -
World Journal of Clinical Cases Apr 2022Melanomas are malignant tumors that can occur in different body parts or tissues such as the skin, mucous membrane, uvea, and pia mater. Long non-coding RNAs (lncRNAs)...
BACKGROUND
Melanomas are malignant tumors that can occur in different body parts or tissues such as the skin, mucous membrane, uvea, and pia mater. Long non-coding RNAs (lncRNAs) are key factors in the occurrence and development of many malignant tumors, and are involved in the prognosis of some patients.
AIM
To identify autophagy-related lncRNAs in melanoma that are crucial for the diagnosis, treatment, and prognosis of melanoma patients.
METHODS
We retrieved transcriptome expression profiles and clinical information of 470 melanoma patients from The Cancer Genome Atlas (TCGA) database. Then, we identified autophagy-related genes in the Human Autophagy Database. Using R, coexpression analysis of lncRNAs and autophagy-related genes was conducted to obtain autophagy-related lncRNAs and their expression levels. We also performed univariate and multivariate Cox proportional risk analyses on the obtained datasets, to systematically evaluate the prognostic value of autophagy-related lncRNAs in melanoma. Fifteen autophagy-related lncRNAs were identified and an autophagy-related prognostic signature for melanoma was established. The Kaplan-Meier and univariate and multivariate Cox regression analyses were used to calculate risk scores. Based on the risk scores, melanoma patients were randomly divided into high- and low-risk groups. Receiver operating characteristic curve analysis, dependent on time, was performed to assess the accuracy of the prognostic model. At the same time, we also downloaded the melanoma data sets GSE65904, GSE19234, and GSE78220 from the GENE EXPRESSION OMNIBUS database for model verification. Finally, we performed Gene Set Enrichment Analysis functional annotation, which showed that the low and the high-risk groups had different enriched pathways.
RESULTS
The co-expression network for autophagy-related genes was constructed using R, and 936 lncRNAs related to autophagy were identified. Then, 52 autophagy-related lncRNAs were significantly associated with TCGA melanoma patients' survival by univariate Cox proportional risk analysis ( < 0.01). Further, the 52 autophagy-related lncRNAs mentioned above were analyzed by multivariate Cox analysis with R. Fifteen lncRNAs were selected: LINC01943, AC090948.3, USP30-AS1, AC068282.1, AC004687.1, AL133371.2, AC242842.1, PCED1B-AS1, HLA-DQB1-AS1, AC011374.2, LINC00324, AC018553.1, LINC00520, DBH-AS1, and ITGB2-AS1. The values in all survival analyses using these 15 lncRNAs were < 0.05. These lncRNAs were used to build a risk model based on the risk score. Negative correlations were observed between risk scores and overall survival rate in melanoma patients over time. Additionally, the melanoma risk curve and scatter plot analyses showed that the death number increased along with the increase in the risk score. Overall, we identified and established a new prognostic risk model for melanoma using 15 autophagy-related lncRNAs. The risk model constructed with these lncRNAs can help and guide melanoma patient prognosis predictions and individualized treatments in the future.
CONCLUSION
Overall, the risk model developed based on the 15 autophagy-related lncRNAs can have important prognostic value and may provide autophagy-related clinical targets for melanoma treatment.
PubMed: 35611195
DOI: 10.12998/wjcc.v10.i11.3334 -
ENeuro 2022The migration of neurons from their birthplace to their correct destination is one of the most crucial steps in brain development. Incomplete or incorrect migration...
The migration of neurons from their birthplace to their correct destination is one of the most crucial steps in brain development. Incomplete or incorrect migration yields ectopic neurons, which cause neurologic deficits or are negligible at best. However, the granule cells (GCs) in the cerebellar cortex may challenge this traditional view of ectopic neurons. When animals are born, GCs proliferate near the pia mater and then migrate down to the GC layer located deep in the cerebellar cortex. However, some GC-like cells stay in the molecular layer, a layer between the pia mater and GC layer, even in normal adult animals. These cells were named ectopic GCs nearly 50 years ago, but their abundance and functional properties remain unclear. Here, we have examined GCs in the molecular layer (mGCs) with a specific marker for mature GCs and transgenic mice in which GCs are sparsely labeled with a fluorescent protein. Contrary to the previous assumption that mGCs are a minor neuronal population, we have found that mGCs are as prevalent as stellate or basket cells in the posterior cerebellum. They are produced during a similar period as regular GCs (rGCs), and time-lapse imaging has revealed that mGCs are stably present in the molecular layer. Whole-cell patch-clamp recordings have shown that mGCs discharge action potentials similarly to rGCs. Since axonal inputs differ between the molecular layer and GC layer, mGCs might be incorporated in different micro-circuits from rGCs and have a unique functional role in the cerebellum.
Topics: Animals; Cerebellum; Mice; Mice, Transgenic; Neurons
PubMed: 35584915
DOI: 10.1523/ENEURO.0289-21.2022 -
ACS Applied Bio Materials Jun 2022(MS) is a medicinal herb known worldwide for its beneficial effects due to the several active molecules present in its leaves and flowers. These compounds have shown...
(MS) is a medicinal herb known worldwide for its beneficial effects due to the several active molecules present in its leaves and flowers. These compounds have shown antioxidant and anti-inflammatory properties and thus can be helpful in treatments of burns and chronic wounds, characterized mainly by high levels of free radicals and impairments of the inflammatory response. In this work, we propose bilayer films as wound dressings, based on poly(vinylpyrrolidone) (PVP) and sodium alginate loaded with extracts from leaves and flowers and fabricated by combining solvent-casting and rod-coating methods. The top layer is produced in two different PVP/alginate ratios and loaded with the MS flowers' extract, while the bottom layer is composed of PVP and MS leaves' extract. The bilayers were characterized morphologically, chemically, and mechanically, while they showed superior self-adhesive properties on human skin compared to a commercial skin patch. The materials showed antioxidant activity, release of the bioactive compounds, and water uptake property. Moreover, the anthocyanin content of the flower extract provided the films with the ability to change color when immersed in buffers of different pH levels. In vitro tests using primary keratinocytes demonstrated the biocompatibility of the MS bilayer materials and their capacity to enhance the proliferation of the cells in a wound scratch model. Finally, the best performing MS bilayer sample with a PVP/alginate ratio of 70:30 was evaluated in mice models, showing suitable resorption properties and the capacity to reduce the level of inflammatory mediators in UVB-induced burns when applied to an open wound. These outcomes suggest that the fabricated bilayer films loaded with extracts are promising formulations as active and multifunctional dressings for treating skin disorders.
Topics: Adhesives; Alginates; Animals; Antioxidants; Bandages; Burns; Malva; Mice; Plant Extracts; Resin Cements
PubMed: 35583459
DOI: 10.1021/acsabm.2c00254 -
The Lancet. Diabetes & Endocrinology Jul 2022The association between cortisol secretion and mortality in patients with adrenal incidentalomas is controversial. We aimed to assess all-cause mortality, prevalence of...
Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study.
BACKGROUND
The association between cortisol secretion and mortality in patients with adrenal incidentalomas is controversial. We aimed to assess all-cause mortality, prevalence of comorbidities, and occurrence of cardiovascular events in uniformly stratified patients with adrenal incidentalomas and cortisol autonomy (defined as non-suppressible serum cortisol on dexamethasone suppression testing).
METHODS
We conducted an international, retrospective, cohort study (NAPACA Outcome) at 30 centres in 16 countries. Eligible patients were aged 18 years or older with an adrenal incidentaloma (diameter ≥1 cm) detected between Jan 1, 1996, and Dec 31, 2015, and availability of a 1 mg dexamethasone suppression test result from the time of the initial diagnosis. Patients with clinically apparent hormone excess, active malignancy, or follow-up of less than 36 months were excluded. Patients were stratified according to the 0800-0900 h serum cortisol values after an overnight 1 mg dexamethasone suppression test; less than 50 nmol/L was classed as non-functioning adenoma, 50-138 nmol/L as possible autonomous cortisol secretion, and greater than 138 nmol/L as autonomous cortisol secretion. The primary endpoint was all-cause mortality. Secondary endpoints were the prevalence of cardiometabolic comorbidities, cardiovascular events, and cause-specific mortality. The primary and secondary endpoints were assessed in all study participants.
FINDINGS
Of 4374 potentially eligible patients, 3656 (2089 [57·1%] with non-functioning adenoma, 1320 [36·1%] with possible autonomous cortisol secretion, and 247 [6·8%] with autonomous cortisol secretion) were included in the study cohort for mortality analysis (2350 [64·3%] women and 1306 [35·7%] men; median age 61 years [IQR 53-68]; median follow-up 7·0 years [IQR 4·7-10·2]). During follow-up, 352 (9·6%) patients died. All-cause mortality (adjusted for age, sex, comorbidities, and previous cardiovascular events) was significantly increased in patients with possible autonomous cortisol secretion (HR 1·52, 95% CI 1·19-1·94) and autonomous cortisol secretion (1·77, 1·20-2·62) compared with patients with non-functioning adenoma. In women younger than 65 years, autonomous cortisol secretion was associated with higher all-cause mortality than non-functioning adenoma (HR 4·39, 95% CI 1·93-9·96), although this was not observed in men. Cardiometabolic comorbidities were significantly less frequent with non-functioning adenoma than with possible autonomous cortisol secretion and autonomous cortisol secretion (hypertension occurred in 1186 [58·6%] of 2024 patients with non-functioning adenoma, 944 [74·0%] of 1275 with possible autonomous cortisol secretion, and 179 [75·2%] of 238 with autonomous cortisol secretion; dyslipidaemia occurred in 724 [36·2%] of 1999 patients, 547 [43·8%] of 1250, and 123 [51·9%] of 237; and any diabetes occurred in 365 [18·2%] of 2002, 288 [23·0%] of 1250, and 62 [26·7%] of 232; all p values <0·001).
INTERPRETATION
Cortisol autonomy is associated with increased all-cause mortality, particularly in women younger than 65 years. However, until results from randomised interventional trials are available, a conservative therapeutic approach seems to be justified in most patients with adrenal incidentaloma.
FUNDING
Deutsche Forschungsgemeinschaft, Associazione Italiana per la Ricerca sul Cancro, Università di Torino.
Topics: Adenoma; Adrenal Gland Neoplasms; Cohort Studies; Dexamethasone; Female; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Retrospective Studies
PubMed: 35533704
DOI: 10.1016/S2213-8587(22)00100-0 -
Investigative Ophthalmology & Visual... Apr 2022Nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with a thickened choroid at the optic nerve head (ONH). Here, we use computational modeling...
PURPOSE
Nonarteritic anterior ischemic optic neuropathy (NAION) has been associated with a thickened choroid at the optic nerve head (ONH). Here, we use computational modeling to better understand how choroidal expansion and choroidal geometry influence tissue deformation within the ONH relative to intraocular pressure (IOP) and intracranial pressure (ICP) effects.
METHODS
Using a model of the posterior eye that included the sclera, peripapillary sclera, annular ring, pia mater, dura mater, neural tissues, Bruch's membrane, choroid, and lamina cribrosa, we examined how varying material properties of ocular tissues influenced ONH deformations under physiological and supra-physiological, or "pathological," conditions. We considered choroidal expansion (c. 35 µL of expansion), elevated IOP (30 mm Hg), and elevated ICP (20 mm Hg), and calculated peak strains in the ONH relative to a baseline condition representing an individual in the upright position.
RESULTS
Supra-physiological choroidal expansion had the largest impact on strains in the prelaminar neural tissue. In addition, compared to a tapered choroid, a "blunt" choroid insertion at the ONH resulted in higher strains. Elevated IOP and ICP caused the highest strains within the lamina cribrosa and retrolaminar neural tissue, respectively.
CONCLUSIONS
Acute choroidal expansion caused large deformations of the ONH and these deformations were impacted by choroid geometry. These results are consistent with the concept that compartment syndrome due to the choroid geometry and/or expansion at the ONH contributes to NAION. Prolonged deformations due to supra-physiological loading may induce a mechanobiological response or ischemia, highlighting the potential impact of choroidal expansion on biomechanical strains in the ONH.
Topics: Choroid; Finite Element Analysis; Humans; Optic Disk; Optic Nerve Diseases; Optic Neuropathy, Ischemic
PubMed: 35481840
DOI: 10.1167/iovs.63.4.23 -
Brain Stimulation 2022When modeling transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) in the brain, the meninges - dura, arachnoid, and pia mater - are...
BACKGROUND
When modeling transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) in the brain, the meninges - dura, arachnoid, and pia mater - are often neglected due to high computational costs.
OBJECTIVE
We investigate the impact of the meningeal layers on the cortical electric field in TES and TMS while considering the headreco segmentation as the base model.
METHOD
We use T1/T2 MRI data from 16 subjects and apply the boundary element fast multipole method with adaptive mesh refinement, which enables us to accurately solve this problem and establish method convergence at reasonable computational cost. We compare electric fields in the presence and absence of various meninges for two brain areas (M1 and DLPFC) and for several distinct TES and TMS setups.
RESULTS
Maximum electric fields in the cortex for focal TES consistently increase by approximately 30% on average when the meninges are present in the CSF volume. Their effect on the maximum field can be emulated by reducing the CSF conductivity from 1.65 S/m to approximately 0.85 S/m. In stark contrast to that, the TMS electric fields in the cortex are only weakly affected by the meningeal layers and slightly (∼6%) decrease on average when the meninges are included.
CONCLUSION
Our results quantify the influence of the meninges on the cortical TES and TMS electric fields. Both focal TES and TMS results are very consistent. The focal TES results are also in a good agreement with a prior relevant study. The solver and the mesh generator for the meningeal layers (compatible with SimNIBS) are available online.
Topics: Brain; Humans; Meninges; Surgical Mesh; Transcranial Direct Current Stimulation; Transcranial Magnetic Stimulation
PubMed: 35447379
DOI: 10.1016/j.brs.2022.04.009 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2022Unlike the usual peripheral nerve, the optic nerve accompanies a thick "dural sheath," a thin "sheath of pia mater" (SPM), and multiple "septa," which divides the nerve...
Unlike the usual peripheral nerve, the optic nerve accompanies a thick "dural sheath," a thin "sheath of pia mater" (SPM), and multiple "septa," which divides the nerve fibers into fascicles. We collected specimens from 25 adult cadavers and 15 fetuses and revisited the histological architecture of the optic and oculomotor nerves. In the optic chiasma, the meningeal layer of the dura joins the pia to form a thick SPM, and the periosteum of the sphenoid is continuous with the dural sheath at the orbital exit of the bony optic canal. The septa appeared as a cluster of irregularly arrayed fibrous plates in the intracranial course near the chiasma. Thus, the septa were not derived from either the SPM or the dural sheath. In the orbit, the central artery of the retina accompanies collagenous fibers from the dural sheath and the SPM to provide the vascular sheath in the optic nerve. These connective tissue configurations were the same between adult and fetal specimens. At the optic disk, the dural sheath and SPM merged with the sclera, whereas the septa appeared to end at the lamina cribrosa. However, in fetuses without lamina cribrosa, the septa extend into the nerve fiber layer of the retina. The SPM and septa showed strong elastin immunoreactivity, in contrast to the absence of reactivity in the sheaths of the oculomotor nerve. Each S100 protein-positive Schwann sheath of the oculomotor nerve was surrounded by collagenous endoneurium. Glial fibrillary acidic protein-positive astrocytes showed a linear arrangement along the septa.
Topics: Adult; Humans; Optic Nerve; Optic Disk; Connective Tissue; Cadaver; Fetus
PubMed: 35358354
DOI: 10.1002/ar.24925 -
Nature Communications Feb 2022Inflammation triggers secondary brain damage after stroke. The meninges and other CNS border compartments serve as invasion sites for leukocyte influx into the brain... (Observational Study)
Observational Study
Inflammation triggers secondary brain damage after stroke. The meninges and other CNS border compartments serve as invasion sites for leukocyte influx into the brain thus promoting tissue damage after stroke. However, the post-ischemic immune response of border compartments compared to brain parenchyma remains poorly characterized. Here, we deeply characterize tissue-resident leukocytes in meninges and brain parenchyma and discover that leukocytes respond differently to stroke depending on their site of residence. We thereby discover a unique phenotype of myeloid cells exclusive to the brain after stroke. These stroke-associated myeloid cells partially resemble neurodegenerative disease-associated microglia. They are mainly of resident microglial origin, partially conserved in humans and exhibit a lipid-phagocytosing phenotype. Blocking markers specific for these cells partially ameliorates stroke outcome thus providing a potential therapeutic target. The injury-response of myeloid cells in the CNS is thus compartmentalized, adjusted to the type of injury and may represent a therapeutic target.
Topics: Aged; Aged, 80 and over; Animals; Brain; Disease Models, Animal; Female; Gene Knock-In Techniques; Humans; Infarction, Middle Cerebral Artery; Male; Mice; Microglia; Middle Aged; Myeloid Cells; Neuroinflammatory Diseases; Pia Mater
PubMed: 35177618
DOI: 10.1038/s41467-022-28593-1 -
WIREs Mechanisms of Disease Jul 2022Arterial collateralization, as determined by leptomeningeal anastomoses or pial collateral vessels, is a well-established vital player in cerebral blood flow restoration... (Review)
Review
Arterial collateralization, as determined by leptomeningeal anastomoses or pial collateral vessels, is a well-established vital player in cerebral blood flow restoration and neurological recovery from ischemic stroke. A secondary network of cerebral collateral circulation apart from the Circle of Willis, exist as remnants of arteriole development that connect the distal arteries in the pia mater. Recent interest lies in understanding the cellular and molecular adaptations that control the growth and remodeling, or arteriogenesis, of these pre-existing collateral vessels. New findings from both animal models and human studies of ischemic stroke suggest a multi-factorial and complex, temporospatial interplay of endothelium, immune and vessel-associated cell interactions may work in concert to facilitate or thwart arteriogenesis. These valuable reports may provide critical insight into potential predictors of the pial collateral response in patients with large vessel occlusion and may aid in therapeutics to enhance collateral function and improve recovery from stroke. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology.
Topics: Animals; Cerebrovascular Circulation; Collateral Circulation; Humans; Ischemic Stroke; Meninges; Stroke
PubMed: 35118835
DOI: 10.1002/wsbm.1553