PATH-46. DIAGNOSTIC IMPACT OF THE CNS TUMOR METHYLATION PROFILING IN A NEUROPATHOLOGY CONSULT PRACTICE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi125-vi126
Author(s):  
Zhichao Wu ◽  
Zied Abdullaev ◽  
Drew Pratt ◽  
Hye-Jung Chung ◽  
Shannon Skarshaug ◽  
...  
Keyword(s):  
Consecutive Series ◽  
Cns Tumor ◽  
Tumor Purity ◽  
The Central Nervous System ◽  
Orthogonal Methods ◽  
New Diagnosis ◽  
Tumor Types ◽  
The Impact ◽  
Methylation Signal ◽  
Methylation Profiling

Abstract DNA methylation profiling coupled with the application of CNS tumor methylation classifier has contributed to precise and accurate diagnostics for a range of tumor types involving the central nervous system. The impact and characteristics of methylation profiling on tumor diagnosis has not been fully assessed in the setting of neuropathology consultation practice. A consecutive series of 1,258 surgical neuropathology samples obtained primarily in a consultation practice were profiled over 2-year period and analyzed using the DKFZ/Heidelberg CNS tumor methylation classifier. Among the 1,045 cases received from outside institutions for consultation, the classifier was able to refine a histologically diagnosed entity (e.g. medulloblastoma) in 13.3% (n = 139) cases. A substantially new diagnosis was able to be rendered in an additional 17.9% (n = 187) cases, many of which could be confirmed using orthogonal methods. A “suggestive” (0.30-0.84) classifier score was found in 23% (242) cases and we found that complementary methods (UMAP, t-SNE and nearest-neighbors) were able to resolve this uncertainty in 118 cases. We found tumor purity significantly associated with varied classifier score (p = 1.53e-11). Computational tumor purity adjustment by deconvolution on a subset of gliomas provided a proof-of-concept to resolve diagnostics in the setting of low tumor purity. Overall, this work directly assesses the benefit of methylation classification in a set of diagnostically challenging CNS tumors, addresses tumor purity diminished methylation signal and provides complementary approaches to address diagnostics in cases of low-confidence classifier scores.

scholarly journals Co-Deregulated miRNA Signatures in Childhood Central Nervous System Tumors: In Search for Common Tumor miRNA-Related Mechanics

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3028
Author(s):  
George I. Lambrou ◽  
Apostolos Zaravinos ◽  
Maria Braoudaki
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cns Tumors ◽  
Normal Brain ◽  
Cns Tumor ◽  
Different Types ◽  
Receiver Operator Curve Analysis ◽  
The Central Nervous System ◽  
Tumor Types ◽  
Operator Curve

Despite extensive experimentation on pediatric tumors of the central nervous system (CNS), related to both prognosis, diagnosis and treatment, the understanding of pathogenesis and etiology of the disease remains scarce. MicroRNAs are known to be involved in CNS tumor oncogenesis. We hypothesized that CNS tumors possess commonly deregulated miRNAs across different CNS tumor types. Aim: The current study aims to reveal the co-deregulated miRNAs across different types of pediatric CNS tumors. Materials: A total of 439 CNS tumor samples were collected from both in-house microarray experiments as well as data available in public databases. Diagnoses included medulloblastoma, astrocytoma, ependydoma, cortical dysplasia, glioblastoma, ATRT, germinoma, teratoma, yoc sac tumors, ocular tumors and retinoblastoma. Results: We found miRNAs that were globally up- or down-regulated in the majority of the CNS tumor samples. MiR-376B and miR-372 were co-upregulated, whereas miR-149, miR-214, miR-574, miR-595 and miR-765 among others, were co-downregulated across all CNS tumors. Receiver-operator curve analysis showed that miR-149, miR-214, miR-574, miR-595 and miR765 could distinguish between CNS tumors and normal brain tissue. Conclusions: Our approach could prove significant in the search for global miRNA targets for tumor diagnosis and therapy. To the best of our knowledge, there are no previous reports concerning the present approach.

scholarly journals SARS-CoV-2 and the Nervous System: From Clinical Features to Molecular Mechanisms

2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  
Keyword(s):  
Nervous System ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Neurological Complications ◽  
Neurological Manifestations ◽  
Wide Range ◽  
Inflammatory State ◽  
Acute Polyneuropathy ◽  
The Central Nervous System ◽  
The Impact

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.

Speech Methodologies in Cleft Palate Assessment: A Pilot Project to Compare Two Phonetically Different Sentence Sets

2013 ◽  
Vol 20 (1) ◽  
pp. 49-72
Author(s):  
Jennie Smith ◽  
Tim Pring ◽  
Debbie Sell
Keyword(s):  
Cleft Palate ◽  
Pilot Project ◽  
Wilcoxon Test ◽  
Consecutive Series ◽  
Video Recordings ◽  
Significant Difference ◽  
The Difference ◽  
Audio Video ◽  
Age Range ◽  
The Impact

Objective: To investigate the impact of the phonetic content of two sentence sets on speech outcomes, specifically the effects of nasal phonemes. Method: Audio-video recordings of a consecutive series of 15 participants (age range 4–22 years), with cleft palate (syndromic or non-syndromic), with and without velopharyngeal dysfunction were taken. Participants repeated Sentence Set 1 (with nasals across sentences) and Sentence Set 2 (without nasals except the three nasal target sentences) during a routine speech recording. Two experienced Specialist Speech and Language Therapists, blinded to the study’s purpose, analyzed participants’ speech using the Cleft Audit Protocol for Speech-Augmented (CAPS-A). On day 1, recordings included Sentence Set 1. On day 2, 23 days later, recordings included Sentence Set 2. Main results: The difference between Sentence Set 1 and Sentence Set 2 ‘total scores’ (sum of scores on all CAPS-A parameters) was significant. The Pearson Product Moment showed high correlation. A Wilcoxon test revealed a significant difference between Sets 1 and 2 on the hypernasality parameter, and this alone accounted for the significant difference in total scores. Conclusion: The inclusion or exclusion of nasal consonants in the sentence set significantly affected perceptual ratings of hypernasality but none of the other CAPS-A parameters, highlighting the need for further investigation into perceptual nasality ratings.

scholarly journals Lasting effects of prenatal exposure to Cannabis in the retina of the offspring: an experimental study in mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Paulo Roberto Arruda Zantut ◽  
Mariana Matera Veras ◽  
Sarah Gomes Menezes Benevenutto ◽  
Angélica Mendonça Vaz Safatle ◽  
Ricardo Augusto Pecora ◽  
...  
Keyword(s):  
Young Adult ◽  
Light Microscopy ◽  
Prenatal Exposure ◽  
Structural Changes ◽  
Volume Fraction ◽  
Clinical Care ◽  
Retinal Layer ◽  
Exposed Population ◽  
The Central Nervous System ◽  
The Impact

Abstract Background Prenatal exposure to Cannabis is a worldwide growing problem. Although retina is part of the central nervous system, the impact of maternal Cannabis use on the retinal development and its postnatal consequences remains unknown. As the prenatal period is potentially sensitive in the normal development of the retina, we hypothesized that recreational use of Cannabis during pregnancy may alter retina structure in the offspring. To test this, we developed a murine model that mimics human exposure in terms of dose and use. Methods Pregnant BalbC mice were exposed daily for 5 min to Cannabis smoke (0.2 g of Cannabis) or filtered air, from gestational day 5 to 18 (N = 10/group). After weaning period, pups were separated and examined weekly. On days 60, 120, 200, and 360 after birth, 10 pups from each group were randomly selected for Spectral Domain Optical Coherence Tomography (SD-OCT) analysis of the retina. All retina layers were measured and inner, outer, and total retina thickness were calculated. Other 37 mice from both groups were sacrificed on days 20, 60, and 360 for retinal stereology (total volume of the retina and volume fraction of each retinal layer) and light microscopy. Means and standard deviations were calculated and MANOVA was performed. Results The retina of animals which mother was exposed to Cannabis during gestation was 17% thinner on day 120 (young adult) than controls (P = 0.003) due to 21% thinning of the outer retina (P = 0.001). The offspring of mice from the exposed group presented thickening of the IS/OS in comparison to controls on day 200 (P < 0.001). In the volumetric analyzes by retinal stereology, the exposed mice presented transitory increase of the IS/OS total volume and volume fraction on day 60 (young adult) compared to controls (P = 0.008 and P = 0.035, respectively). On light microscopy, exposed mice presented thickening of the IS/OS on day 360 (adult) compared to controls (P = 0.03). Conclusion Gestational exposure to Cannabis smoke may cause structural changes in the retina of the offspring that return to normal on mice adulthood. These experimental evidences suggest that children and young adults whose mothers smoked Cannabis during pregnancy may require earlier and more frequent clinical care than the non-exposed population.

Results of Embolization Used as the First Treatment Choice in a Consecutive Nonselected Population of Ruptured Aneurysms: Clinical Results of the Clarity GDC Study

Neurosurgery ◽  
2011 ◽  
Vol 69 (4) ◽  
pp. 837-842 ◽  
Author(s):  
◽  
Christophe Cognard ◽  
Laurent Pierot ◽  
René Anxionnat ◽  
Frédéric Ricolfi
Keyword(s):  
Clinical Results ◽  
Morbidity And Mortality ◽  
World Federation ◽  
Consecutive Series ◽  
Ruptured Aneurysms ◽  
First Choice ◽  
International Subarachnoid Aneurysm Trial ◽  
Treatment Morbidity ◽  
Intraoperative Rupture ◽  
The Impact

Abstract BACKGROUND: The International Subarachnoid Aneurysm Trial (ISAT) showed that for ruptured aneurysms suitable for both techniques, coiling should be the first-choice treatment. Only a small proportion of patients (22%) with ruptured aneurysms were included in that trial. Operators were selected on their experience. One could then criticize the impact of the ISAT on clinical practice as a result of recruitment biases and operators' selection. OBJECTIVE: To evaluate the morbidity and mortality of coiling when used as first-choice treatment in a consecutive population of patients with ruptured aneurysms treated by nonselected operators. METHODS: Thirty-four operators from 19 French centers treated 405 patients with GDC coils from November 2006 to July 2007. The method of treatment was not prespecified. RESULTS: World Federation of Neurological Societies grade at admission was I/II in 65.7% and IV/V in 30.6% of patients. At the 3- to 6-month follow-up, 23.3% of patients were dependent or dead. Thromboembolic events and intraoperative rupture resulted in permanent deficit in 13 (3.2%) and 2 (0.5%), respectively, and death in 4 (1.0%) and 0. Early rebleeding occurred in 2 patients (0.5%) with 2 subsequent deaths. Permanent treatment morbidity and mortality were 3.7 % and 1.5 %, respectively. CONCLUSION: Clinical results of the multicenter prospective Clarity registry show that when coiling is performed as first-intention treatment in a consecutive series of nonselected ruptured aneurysms by nonselected operators, clinical results are similar to those of the ISAT.

scholarly journals Validation and cross-cultural adaptation of sexual dysfunction modified scale in multiple sclerosis for Brazilian population

2015 ◽  
Vol 73 (8) ◽  
pp. 681-687 ◽  
Author(s):  
Raquel Ataíde Peres da Silva ◽  
Guilherme Sciascia do Olival ◽  
Lívia Palma Stievano ◽  
Vania Balardin Toller ◽  
Sergio Semeraro Jordy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Sexual Dysfunction ◽  
Cultural Adaptation ◽  
Chronic Inflammatory Disease ◽  
Cross Cultural ◽  
Brazilian Population ◽  
Control Group ◽  
Cross Cultural Adaptation ◽  
The Central Nervous System ◽  
The Impact

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). These patients suffer from various comorbidities, including sexual dysfunction (SD). The lesions of MS may affect regions of the CNS along the pathway of sexual response. The Multiple Sclerosis Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a scale that assesses sexual dysfunction. Adapt and validate the MSISQ-19 to Brazilian patients with MS. 204 individuals were evaluated, 134 patients with MS and 70 healthy persons for the control group. It was determined reproducibility, validity, internal consistency and sensitivity of the MSISQ-19-BR. Among patients with MS, 54.3% of male and 71.7% of female presented some kind of SD. In the control group the results were 12.5% and 19.5%, respectively. The MSISQ-19-BR is reproducible, reliable and valid for the Brazilian population and may be used as a tool for assessing the impact of sexual dysfunction in patients with MS.

Effects of CSF Properties on Brain Response Under Impact Loading

2009 ◽  
Author(s):  
M. S. Chafi ◽  
V. Dirisala ◽  
G. Karami ◽  
M. Ziejewski
Keyword(s):  
Human Head ◽  
Brain Response ◽  
Pia Mater ◽  
Mechanical Shocks ◽  
The Central Nervous System ◽  
Simultaneous Loading ◽  
The Impact ◽  
Impact Experiments ◽  
The Brain

In the central nervous system, the subarachnoid space is the interval between the arachnoid membrane and the pia mater. It is filled with a clear, watery liquid called cerebrospinal fluid (CSF). The CSF buffers the brain against mechanical shocks and creates buoyancy to protect it from the forces of gravity. The relative motion of the brain due to a simultaneous loading is caused because the skull and brain have different densities and the CSF surrounds the brain. The impact experiments are usually carried out on cadavers with no CSF included because of the autolysis. Even in the cadaveric head impact experiments by Hardy et al. [1], where the specimens are repressurized using artificial CSF, this is not known how far this can replicate the real functionality of CSF. With such motivation, a special interest lies on how to model this feature in a finite element (FE) modeling of the human head because it is questionable if one uses in vivo CSF properties (i.e. bulk modulus of 2.19 GPa) to validate a FE human head against cadaveric experimental data.

scholarly journals METHODOLOGICAL PROBLEMS OF THE MATHEMATICAL ESTIMATION OF THE IMPACT OF METEOROLOGICAL FACTORS ON ADAPTIVE FUNCTIONS OF THE HUMAN

2019 ◽  
Vol 96 (3) ◽  
pp. 253-257
Author(s):  
Nurlan K. Smagulov ◽  
A. A. Adilbekova
Keyword(s):  
High School ◽  
Mathematical Analysis ◽  
Meteorological Factors ◽  
Meteorological Data ◽  
Correlation Coefficients ◽  
Dose Effect ◽  
Output Factors ◽  
The Central Nervous System ◽  
Methodological Problems ◽  
The Impact

The work is dedicated to methodological problems of the mathematical assessment of the impact of meteorological factors on the adaptive function of the teachers of the High School Institutions. Objects of research. Male teachers of the High School Institution, aged of from 24 to 49 years. Meteorological data were evaluated during the investigation of anthropometric indices of height and weight, individual-typological features and the physiological assessment of the central nervous system, cardiovascular system of the High School teachers. Statistical analysis was performed with the use of Statistica 6.0 package and special statistical software. Paired correlation coefficients obtained as a result of calculation were used to estimate the proportion of the influence of input factors (arguments) on the output factors (functions). A mathematical analysis has allowed to reveal leading meteorological factors that cause a certain level of functional exhaustion during the investigated period. The use of a non-linear correlation analysis allowed to enhance significantly the ability for analytical processing of the results, increase of the effectiveness and the possibility of interpreting the interaction of factors in achieving optimal adaptation of teachers in the working process and to identify the role of meteorological factors in this process. Knowledge of leading factors and the percentage of their contribution to the functional state allowed to give the more accurate assessment of stress to the organism in specific circumstances. The ultimate aim of the mathematical analysis should be not only to find the critical value defined the priority factor characterizing the degree of of information load, but the critical combination of all priority factors causing disruption and the beginning of “start-up” adaptation process in the system “dose-effect. “

scholarly journals Effect of Remdesivir on COVID-19 PCR Positivity and Cycle Threshold in Kidney Transplant Recipients

2021 ◽  
Vol 2 (3) ◽  
pp. 291-293
Author(s):  
Ryan J. Winstead ◽  
Johanna Christensen ◽  
Sara Sterling ◽  
Megan Morales ◽  
Dhiren Kumar ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cycle Threshold ◽  
Transplant Patients ◽  
Kidney Transplant Patients ◽  
Polymerase Chain ◽  
New Diagnosis ◽  
The Impact ◽  
Median Change

Information regarding Coronavirus disease 2019 in the transplant population is lacking. Recently it has been suggested that cycle threshold values obtained on polymerase chain reaction tests may serve as a marker of disease severity with lower values (i.e., higher viral load) being associated with higher mortality. This study was done to assess the impact of remdesivir use on the time to a negative COVID-19 PCR as well as the degree of change between two Ct’s based on treatment. A total of 30 kidney transplant patients with a new diagnosis of COVID-19 were assessed. Serial PCR results were followed from the time of diagnosis then every 2–4 weeks until negative. In patients who received remdesivir immediately after COVID-19 confirmation compared to no remdesivir, time to negative PCR was not statistically different with a median duration of 57 days in both groups (p = 0.369). The change in the Ct between the first and the second PCR test was also not statistically different between groups with a median change of 18.4 cycles in the remdesivir group and 15.7 cycles without remdesivir (p = 0.516). The results of this small single-center analysis suggest that remdesivir may not be beneficial in shortening time to a negative COVID-19 PCR.

scholarly journals The variable monoaminergic outcomes of cleaner fish brains when facing different social and mutualistic contexts

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4830 ◽  
Author(s):  
Murilo S. de Abreu ◽  
João P.M. Messias ◽  
Per-Ove Thörnqvist ◽  
Svante Winberg ◽  
Marta C. Soares
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Social Behaviour ◽  
Visual Assessment ◽  
Physical Contact ◽  
Specific Response ◽  
Dopaminergic Activity ◽  
Cleaner Fish ◽  
The Central Nervous System ◽  
The Impact

The monoamines serotonin and dopamine are important neuromodulators present in the central nervous system, known to be active regulators of social behaviour in fish as in other vertebrates. Our aim was to investigate the region-specific brain monoaminergic differences arising when individual cleaners face a client (mutualistic context) compared to when they are introduced to another conspecific (conspecific context), and to understand the relevance of visual assessment compared to the impact of physical contact with any partner. We demonstrated that serotoninergic activity at the diencephalon responds mostly to the absence of physical contact with clients whereas cerebellar dopaminergic activity responds to actual cleaning engagement. We provide first insights on the brain’s monoaminergic (region-specific) response variations, involved in the expression of cleaner fishes’ mutualistic and conspecific behaviour. These results contribute to a better understanding of the monoaminergic activity in accordance to different socio-behavioural contexts.

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