Giant cell tumor of the posterior arc of the rib: A case report and literature of review.

INTRODUCTION AND IMPORTANCE: Giant cell tumors of bone (GCTB) are infrequent tumors that usually impact the epiphyses of long bones and uncommonly manifest in the ribs. Herein, we report a case of asymptomatic GCTB directly invading the lung tissue. CASE PRESENTATION: A 36-year-old man was referred to our emergency department with only left chest pain. Computed tomography revealed a large heterogeneous solid cystic mass in the left lung apex and amorphous calcification and distraction in the posterior part of the left fourth rib. Histological examination also exhibited that the GCTB originated from the rib. The patient underwent an en-bloc resection with no recurrence in his one-year follow-up. CLINICAL DISCUSSION: GCTB is characterized by osteoclast-like multinucleated giant cells and can exhibit aggressive local behavior. GCTB in the rib is rare, mainly found in the posterior arc. Radiographic features include lytic lesions with bone remodeling, often seen eccentrically in long bone epiphyses. Aggressive tumors may show cortical destruction and soft tissue extension. Surgery is often recommended for GCTB management, aiming for complete resection with sufficient surgical margins. CONCLUSION: The absence of well-defined diagnostic criteria hinders the accurate diagnosis of GCTB, making a comprehensive assessment through radiological and histological examinations crucial. Upon physical examination, GCTB should be considered in the differential diagnosis for mediastinal lesions, regardless of their size. Furthermore, surgical removal can be taken into account as the primary treatment strategy for tumors that originate from the posterior arc of the ribs, such as GCTB.

Efficacy and Challenges: Minimally Invasive Procedures for Trigeminal Neuralgia Treatment in Multiple Sclerosis - A Systematic Review and Meta-Analysis.

INTRODUCTION: Trigeminal neuralgia (TGN) poses a therapeutic challenge, particularly within the context of multiple sclerosis (MS). This study aimed to conduct a comprehensive meta-analysis and systematic review of four less-invasive treatment modalities for TGN in MS patients, namely, gamma knife radiosurgery (GKRS), glycerol rhizotomy (GR), balloon compression (BC), and radiofrequency ablation (RFA). METHODS: Single-armed meta-analyses were employed to assess the overall efficacy of each treatment, while double-armed analyses compared the efficacy between different treatment options in double-armed studies. Outcome evaluations included acute pain relief (within 1 month post-procedure), recurrence rates throughout 18 months of follow-up, and reported complication rates. RESULTS: The meta-analysis revealed diverse outcomes for each intervention. GKRS demonstrated favorable outcomes, achieving a 77% success rate in alleviating pain among a pooled cohort of 863 patients, reinforcing its status as a viable therapeutic option. Additionally, GR, BC, and RFA exhibited efficacy, with success rates of 77%, 71%, and 80%, respectively, based on outcomes observed in 611, 385, and 203 patients. Double-armed analyses highlighted distinctions between the treatments, providing nuanced insights for clinical decision-making. CONCLUSION: This meta-analysis provides a comprehensive overview of less-invasive treatments for TGN in MS patients. GKRS emerges as a leading option with comparable efficacy and fewer complications. However, the study underscores the nuanced efficacy and considerations associated with GR, BC, and RFA. The findings offer valuable insights for clinicians navigating treatment choices in this challenging patient population, considering acute pain relief, recurrence rates, and complication profiles.

The burden of traumatic brain injury on caregivers: exploring the predictive factors in a multi-centric study.

BACKGROUND: Traumatic brain injury (TBI) is a significant cause of mortality and morbidity worldwide. With survivors often exhibiting degrees of function loss, a significant burden is exerted on their caregivers. The purpose of this study was to explore the predictive factors of caregiver burden among caregivers of patients with TBI. METHODS: Sixty-eight family members of individuals with a TBI who had been admitted to three hospitals were assessed in terms of caregiver burden using the Zarit Burden Interview. The association of caregiver burden with patients' baseline cognitive function according to the Montreal Cognitive Assessment (MoCA) test, as well as caregivers' sociodemographic characteristics, were evaluated using multiple regression analysis. RESULTS: Based on the multiple regression model, the MoCA score of the patients (std ß=-0.442, p < 0.001), duration of caregiving (std ß = 0.228, p = 0.044), and higher education of the caregivers (std ß = 0.229, p = 0.038) were significant predictors of caregiver burden. CONCLUSION: Overall, our findings highlight the importance of taking caregivers' psychosocial needs into account. Long-term caregivers of TBI patients with cognitive impairment should be viewed as vulnerable individuals who could benefit from psychosocial intervention programs, to improve their well-being and enabling them to enrich their care of the TBI patient.

Empty sella in somatotropic pituitary adenomas; a series of 23 cases.

Purpose: We aimed to investigate empty sella syndrome in somatotrophic pituitary adenoma for possible etiology, complications, and treatment options. Method: Among over 2,000 skull base masses that have been managed in our center since 2013, we searched for growth hormone-producing adenomas. Clinical, surgical, and imaging data were retrospectively collected from hospital records to check for sella that lacked pituitary tissue on routine imaging. Result: In 220 somatotrophic adenomas, 23 patients had an empty sella with surgical and follow-up data. The mean age of the sample was 46 years with the same male-to-female ratio. Five cases had partial empty sella and the rest were complete empty sellas. The most common simultaneous hormonal disturbance was high prolactin levels. Six had adenoma invasion into the clivus or sphenoid sinus and 10 had cavernous sinus intrusion. Peri-operative low-flow and high-flow cerebrospinal fluid (CSF) leaks were encountered in one and two patients, respectively, which were successfully sealed by abdominal fat. The majority of cases required growth hormone replacement therapy while it was controlled without any replacement therapy in nine patients. No pituitary hormonal disturbance occurred after transsphenoidal surgery except for hypothyroidism in one patient. Conclusion: An empty sella filled with fluid can be detected frequently in pituitary adenomas, especially in the setting of acromegaly. The pituitary gland may be pushed to the roof of the sella and might be visible as a narrow rim on imaging or may be detected in unusual places out of the sella. The pathophysiology behind such finding originates from soft and hard tissue changes and CSF pressure alternations during abundant growth hormone production.

Glioma Tumor Grading Using Radiomics on Conventional MRI: A Comparative Study of WHO 2021 and WHO 2016 Classification of Central Nervous Tumors.

BACKGROUND: Glioma grading transformed in World Health Organization (WHO) 2021 CNS tumor classification, integrating molecular markers. However, the impact of this change on radiomics-based machine learning (ML) classifiers remains unexplored. PURPOSE: To assess the performance of ML in classifying glioma tumor grades based on various WHO criteria. STUDY TYPE: Retrospective. SUBJECTS: A neuropathologist regraded gliomas of 237 patients into WHO 2016 and 2021 from 2007 criteria. FIELD STRENGTH/SEQUENCE: Multicentric 0.5 to 3 Tesla; pre- and post-contrast T1-weighted, T2-weighted, and fluid-attenuated inversion recovery. ASSESSMENT: Radiomic features were selected using random forest-recursive feature elimination. The synthetic minority over-sampling technique (SMOTE) was implemented for data augmentation. Stratified 10-fold cross-validation with and without SMOTE was used to evaluate 11 classifiers for 3-grade (2, 3, and 4; WHO 2016 and 2021) and 2-grade (low and high grade; WHO 2007 and 2021) classification. Additionally, we developed the models on data randomly divided into training and test sets (mixed-data analysis), or data divided based on the centers (independent-data analysis). STATISTICAL TESTS: We assessed ML classifiers using sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC). Top performances were compared with a t-test and categorical data with the chi-square test using a significance level of P < 0.05. RESULTS: In the mixed-data analysis, Stacking Classifier without SMOTE achieved the highest accuracy (0.86) and AUC (0.92) in 3-grade WHO 2021 grouping. The results of WHO 2021 were significantly better than WHO 2016 (P-value<0.0001). In the 2-grade analysis, ML achieved 1.00 in all metrics. In the independent-data analysis, ML classifiers showed strong discrimination between grade 2 and 4, despite lower performance metrics than the mixed analysis. DATA CONCLUSION: ML algorithms performed better in glioma tumor grading based on WHO 2021 criteria. Nonetheless, the clinical use of ML classifiers needs further investigation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Signal enhancement in spark-assisted laser-induced breakdown spectroscopy for discrimination of glioblastoma and oligodendroglioma lesions.

Here, the discrimination of two types of lethal brain cancers, i.e., glioblastoma multiforme (GBM) and oligodendroglioma (OG) are investigated under the laser-induced breakdown spectroscopy (LIBS) and the electrical spark-assisted laser-induced breakdown spectroscopy (SA-LIBS) in order to discriminate the human brain glioma lesions against the infiltrated tissues. It is shown there are notable differences between the plasma emissions over the brain gliomas against those of infiltrated tissues. In fact, a notable enhancement appears in the characteristic emissions in favor of SA-LIBS against those of conventional LIB spectra. Moreover, the plasma properties such as temperature, electron density, and degree of ionization are probed through the data processing of the plasma emissions. The corresponding parameters, taken from SA-LIBS data, attest to be lucidly larger than those of LIBS up to one order of magnitude. In addition, the ionic species such as Mg II characteristic line at 279 nm and caII emission at 393 nm are notably enhanced in favor of SA-LIBS. In general, the experimental evidence verifies that SA-LIBS is beneficial in the discrimination and grading of GBM/OG neoplasia against healthy (infiltrate) tissues in the early stages.

Clinical Effects of Immuno-Oncology Therapy on Glioblastoma Patients: A Systematic Review.

The most prevalent and deadly primary malignant glioma in adults is glioblastoma (GBM), which has a median survival time of about 15 months. Despite the standard of care for glioblastoma, which includes gross total resection, high-dose radiation, and temozolomide chemotherapy, this tumor is still one of the most aggressive and difficult to treat. So, it is critical to find more potent therapies that can help glioblastoma patients have better clinical outcomes. Additionally, the prognosis for recurring malignant gliomas is poor, necessitating the need for innovative therapeutics. Immunotherapy is a rather new treatment for glioblastoma and its effects are not well studied when it is combined with standard chemoradiation therapy. We conducted this study to evaluate different glioblastoma immunotherapy approaches in terms of feasibility, efficacy, and safety. We conducted a computer-assisted literature search of electronic databases for essays that are unique, involve either prospective or retrospective research, and are entirely written and published in English. We examined both observational data and randomized clinical trials. Eighteen studies met the criteria for inclusion. In conclusion, combining immunotherapy with radiochemotherapy and tumor removal is generally possible and safe, and rather effective in the prolongation of survival measures.

ADAMTS9-AS1 Long Non­coding RNA Sponges miR­128 and miR-150 to Regulate Ras/MAPK Signaling Pathway in Glioma.

Glioma is a malignancy of the central nervous system with a poor prognosis. Therefore, the elaboration of its molecular features creates therapeutic opportunities. Looking for the regulatory non-coding RNAs (lncRNAs and miRNAs) that are involved in glioma incidence/progression, RNA-seq analysis introduced upregulated ADAMTS9-AS1 as a bona fide candidate that sponges miR-128 and miR-150 and shows the negative correlation of expression with them. Then, RT-qPCR verified the upregulation of ADAMTS9-AS1 in glioma tissues and cell lines. Furthermore, dual-luciferase assay supported that cytoplasmic ADAMTS9-AS1 is capable of sponging miR-128 and miR-150, which are known as regulators of Ras/MAPK, PI3K, and Wnt pathways. Following the overexpression of ADAMTS9-AS1 in 1321N1 and U87 glioma cells, tyrosine kinase receptors (IGF1R and TrkC), as well as Wnt receptors (Lrp6 and Fzd) were upregulated, detected by RT-qPCR. Furthermore, downstream genes of both Ras/MAPK and Wnt pathways were upregulated. Finally following the ADAMTS9-AS1 overexpression, upregulation of Ras/MAPK and Wnt signaling pathways was verified through western blotting and Top/Fop flash assay, respectively. At the cellular level, ADAMTS9-AS1 overexpression brought about reduced sub-G1 cell population, increased proliferation rate, reduced apoptosis level, increased migration rate, shortened Bax/Bcl2 ratio, induced EMT, and stemness characteristics of transfected cells, detected by flow cytometry, MTT assay, scratch test, and RT-qPCR. Overall, these results introduced ADAMTS9-AS1 as an oncogene that upregulates Ras/MAPK and Wnt pathways through sponging of the miR-128 and miR-150 in glioma cells. The outcome of ADAMTS9-AS1 expression is more aggression of the glioma cells through increased EMT and stemness characteristics. These features candidate ADAMTS9-AS1 locus for glioma therapy. As a result, we discovered the oncogenic properties of ADAMTS9-AS1 in glioma cancer. It sponges miR-128 and miR-150 and subsequently overstimulates RAS/MAPK and Wnt signaling pathways, particularly at the receptors level. Thus, ADAMTS9-AS1 increases proliferation, migration, and stemness in glioma cell lines. A schematic representation showing the functional effect of ADAMTS9-AS1.

Limits on using the clock drawing test as a measure to evaluate patients with neurological disorders.

BACKGROUND: The Clock Drawing Test (CDT) is used as a quick-to-conduct test for the diagnosis of dementia and a screening tool for cognitive impairments in neurological disorders. However, the association between the pattern of CDT impairments and the location of brain lesions has been controversial. We examined whether there is an association between the CDT scores and the location of brain lesions using the two available scoring systems. METHOD: One hundred five patients with brain lesions identified by CT scanning were recruited for this study. The Montreal Cognitive Assessment (MoCA) battery including the CDT were administered to all partcipants. To score the CDT, we used a qualitative scoring system devised by Rouleau et al. (1992). For the quantitative scoring system, we adapted the algorithm method used by Mendes-Santos et al. (2015) based on an earlier study by Sunderland et al. (1989). For analyses, a machine learning algorithm was used. RESULTS: Remarkably, 30% of the patients were not detected by the CDT. Quantitative and qualitative errors were categorized into different clusters. The classification algorithm did not differentiate the patients with traumatic brain injury 'TBI' from non-TBI, or the laterality of the lesion. In addition, the classification accuracy for identifying patients with specific lobe lesions was low, except for the parietal lobe with an accuracy of 63%. CONCLUSION: The CDT is not an accurate tool for detecting focal brain lesions. While the CDT still is beneficial for use with patients suspected of having a neurodegenerative disorder, it should be cautiously used with patients with focal neurological disorders.

Differentiating Glioblastoma Multiforme from Brain Metastases Using Multidimensional Radiomics Features Derived from MRI and Multiple Machine Learning Models.

Due to different treatment strategies, it is extremely important to differentiate between glioblastoma multiforme (GBM) and brain metastases (MET). It often proves difficult to distinguish between GBM and MET using MRI due to their similar appearance on the imaging modalities. Surgical methods are still necessary for definitive diagnosis, despite the importance of magnetic resonance imaging in detecting, characterizing, and monitoring brain tumors. We introduced an accurate, convenient, and user-friendly method to differentiate between GBM and MET through routine MRI sequence and radiomics analyses. We collected 91 patients from one institution, including 50 with GBM and 41 with MET, which were proven pathologically. The tumors separately were segmented on all MRI images (T1-weighted imaging (T1WI), contrast-enhanced T1-weighted imaging (T1C), T2-weighted imaging (T2WI), and fluid-attenuated inversion recovery (FLAIR)) to form the volume of interest (VOI). Eight ML models and feature reduction strategies were evaluated using routine MRI sequences (T1W, T2W, T1-CE, and FLAIR) in two methods with (second model) and without wavelet transform (first model) radiomics. The optimal model was selected based on each model's accuracy, AUC-roc, and F1-score values. In this study, we have achieved the result of 0.98, 0.99, and 0.98 percent for accuracy, AUC-roc, and F1-score, respectively, which have yielded a better result than the first model. In most investigated models, there were significant improvements in the multidimensional wavelets model compared to the non-multidimensional wavelets model. Multidimensional discrete wavelet transform can analyze hidden features of the MRI from a different perspective and generate accurate features which are highly correlated with the model accuracy.

Minimally invasive procedures for hypothalamic hamartoma-related epilepsy: a systematic review and meta-analysis.

OBJECTIVE: Hypothalamic hamartoma (HH) is a rare, nonmalignant, heterotopic developmental malformation that consists of a mixture of normal neurons and glial cells. Resection of HHs has been associated with high rates of mortality and morbidity. Therefore, minimally invasive ablation methods could be the best treatment option for HH. The most frequently used minimally invasive options for HH ablation are radiofrequency thermocoagulation (RFT), laser ablation (LA), and stereotactic radiosurgery. METHODS: To investigate three minimally invasive procedures in the treatment of refractory seizures related to HH, the authors conducted a systematic search in March 2022 in the MEDLINE, Embase, Scopus, and Web of Science databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seizure freedom was the primary outcome of interest. The authors defined seizure freedom as Engel class I or International League Against Epilepsy class 1 or 2 or as the reported term "seizure freedom." The secondary outcome was long-term complications reported in studies. Both random- and fixed-effects models were used to calculate the pooled proportion of seizure freedom and complication rate with 95% confidence intervals. A modified version of the Joanna Briggs Institute (JBI) Critical Appraisal to assess the risk of bias was used. RESULTS: The authors included 15 studies with 422 patients (RFT, n = 190; LA, n = 171; and Gamma Knife Radiosurgery [GKRS], n = 61). Generally, the mean incidences of overall seizure freedom after minimally invasive procedures were 77% (95% CI 0.74-0.81) and 68% (95% CI 0.57-0.79) using fixed- and random-effects models, respectively. The mean incidence of overall seizure freedom after RFT was 69% (95% CI 0.63-0.75), and the mean incidences of overall seizure freedom after LA and GKRS were 87% (95% CI 0.82-0.92) and 44% (95% CI 0.32-0.57), respectively. The total complication rate with minimally invasive procedures was 13% (95% CI 0.01-0.26). The complication rate in each treatment was as follows: 5% (95% CI 0.0-0.12) for RFT, 20% (95% CI 0.0-0.47) for LA, and 22% (95% CI 0-0.65) for GKRS. Meta-regression analysis showed an association between older age and higher complication rates in the LA group. CONCLUSIONS: In this meta-analysis, LA showed superiority in seizure freedom over the other two methods. The complication rate associated with RFT was less than those in the other two methods; however, this difference was not statistically significant.

Histiocytic Sarcoma Involving Cervical Vertebra: A Case Report and Review of the Literature.

Histiocytic sarcoma (HS) is a rare neoplasm composed of cells with immunohistochemical characteristics of mature histiocytes. It can be disseminated or localized and usually involves the skin, spleen, and gastrointestinal tract. Primary involvement of the vertebral column is extremely rare. We report a 29-year-old female who presented with neck pain and had a destructive 35*43*48 mm lesion in C2 with a paravertebral extension. The initial biopsy did not lead to the correct diagnosis. She later developed dysphagia, and the anterior approach was used for tumor decompression. The diagnosis of cervical histiocytic sarcoma was made, and she underwent radiotherapy. The follow-up MRI showed a marked response to radiotherapy. Here, we report the first case of cervical HS, review all cases of vertebral HS, compare patients' characteristics and clinical courses, and discuss diagnostic nuances and treatment options.

State of the Art in Combination Immuno/Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis.

OBJECTIVES: Common origins for brain metastases (BMs) are melanoma, lung, breast, and renal cell cancers. BMs account for a large share of morbidity and mortality caused by these cancers. The advent of new immunotherapeutic treatments has made a revolution in the treatment of cancer patients and particularly, as a new concept, if it is combined with radiotherapy, may lead to considerably longer survival. This systematic review and meta-analysis aimed to evaluate the survival rate and toxicities of such a combination in brain metastases. METHODS: To perform a systematic review of the literature until January 2021 using electronic databases such as PubMed, Cochrane Library, and Embase; the Newcastle-Ottawa Scale was used to evaluate the quality of cohort studies. For data extraction, two reviewers extracted the data blindly and independently. Hazard ratio with 95% confidence interval (CI), fixed-effect model, and inverse-variance method was calculated. The meta-analysis has been evaluated with the statistical software Stata/MP v.16 (The fastest version of Stata). RESULTS: In the first step, 494 studies were selected to review the abstracts, in the second step, the full texts of 86 studies were reviewed. Finally, 28 studies were selected consisting of 1465 patients. The addition of IT to RT in the treatment of brain metastasis from melanoma and non-small-cell lung carcinoma was associated with a 39% reduction in mortality rate and has prolonged overall survival, with an acceptable toxicity profile. The addition of IT to RT compared with RT alone has a hazard ratio of 0.39(95% CI 0.34-0.44). CONCLUSIONS: A combination of immuno/radiotherapy (IR) for the treatment of patients with BMs from melanoma and non-small-cell lung carcinoma has prolonged overall survival and reduced mortality rate, with acceptable toxicity. In terms of timing, RT seems to have the best effect on the result when performed before or simultaneously with immunotherapy.

LINC02381-ceRNA exerts its oncogenic effect through regulation of IGF1R signaling pathway in glioma.

PURPOSE: LncRNAs play essential roles in the cellular and molecular biology of glioma. Some LncRNAs exert their role through sponging miRNAs and regulating multiple signaling pathways. LINC02381 is involved in several cancer types as either oncogene or tumor suppressor. Here, we intended to find the molecular mechanisms of the LINC02381 effect during the glioma progression in related cell lines. METHODS AND RESULTS: RNA-seq data analysis indicated the oncogenic characteristics of LINC02381, and RT-qPCR results confirmed its upregulation compared to normal tissues. Besides its expression was relatively stronger in invasive glioma cell lines. Furthermore, in silico analysis revealed LINC02381 is concentrated in the cytoplasm and predicted its sponging effect against miR-128 and miR-150, which was verified through dual luciferase assay. When LINC02381 was overexpressed in 1321N1, U87, and A172 cell lines, IGF1R and TrkC receptors as well as their downstream pathways (PI3K and RAS/MAPK), were upregulated, detected by RT-qPCR, and verified by western analysis. Consistently, LINC02381 overexpression was followed by an increased proliferation rate of transfected glioma cell lines, detected by flow cytometry and MTT assay, and RT-qPCR. It also resulted in elevated EMT and stemness markers expression level, increased migration rate, and reduced apoptosis rate, detected by RT-qPCR, western analysis, scratch test, and Annexin/PI flow cytometry analysis, respectively. CONCLUSION: The overall results indicated that LINC02381 exerts its oncogenic effect in glioma cells through sponging miR-128 and miR-150 to upregulate the IGF1R signaling pathway. Our results introduce LINC02381 and miR-128, and miR-150 as potential prognosis and therapy targets for the treatment of glioma.

Delayed Effect of Dendritic Cells Vaccination on Survival in Glioblastoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients' long-term survival. This meta-analysis aims to assess the efficacy of DCV for newly diagnosed glioblastoma patients in clinical trials. METHODS: The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: "glioblastoma multiforme", "dendritic cell", "vaccination", "immunotherapy", "immune system", "immune response", "chemotherapy", "recurrence", and "temozolomide". Among the 157 screened, only 15 articles were eligible for the final analysis. RESULTS: Regimens including DCV showed no effect on 6-month progression-free survival (PFS, HR = 1.385, 95% CI: 0.822-2.335, p = 0.673) or on 6-month overall survival (OS, HR = 1.408, 95% CI: 0.882-2.248, p = 0.754). In contrast, DCV led to significantly longer 1-year OS (HR = 1.936, 95% CI: 1.396-2.85, p = 0.001) and longer 2-year OS (HR = 3.670, 95% CI: 2.291-5.879, p = 0.001) versus control groups. Hence, introducing DCV could lead to increased 1 and 2-year survival of patients by 1.9 and 3.6 times, respectively. CONCLUSION: Antitumor regimens including DCV can effectively improve mid-term survival in patients suffering glioblastoma multiforme (GBM), but its impact emerges only after one year from vaccination. These data indicate the need for more time to achieve an anti-GBM immune response and suggest additional therapeutics, such as checkpoint inhibitors, to empower an earlier DCV action in patients affected by a very poor prognosis.

Pathogenic cis p-tau levels in CSF reflects severity of traumatic brain injury.

Traumatic brain injury (TBI) is the main cause of death and disability among young people. Following TBI, immune system activation and cytokine release induce kinase activity and hyperphosphorylation of tau protein, a structural molecule in axonal microtubules. The cis configuration of phosphorylated tau at Th231 is extremely neurotoxic and is having a prion nature, spreads to brain areas as well as CSF.We examined the cerebrospinal fluid (CSF) cis p-tau levels in 32 TBI patients and 5 non-TBI controls to find out the correlation with TBI severity.   CSF samples were drained 5-7 days after TBI and subjected for ELISA analysis with anti cis p-tau and ß-amyloid antibodies.We had no patients with mild TBI, two patients with moderate (6.2%), 23 patients with severe (71.9%), and 7 patients with critical TBI (21.9%). While mean CSF ß-amyloid in TBI and control groups did not show a statistically significant difference, the mean CSF cis p-tau level was significantly higher in the TBI group than the control samples. Also, intergroup analysis demonstrated that CSF cis p-tau levels were statistically different according to the head injury severity.Although CSF cis p-tau increased in the TBI patients, ß-amyloid did not show a significant difference between patients and controls. Also, we observed an obvious negative correlation between CSF cis p-tau levels and GCS scores. Therefore, future researches on suppression of cis P-tau production or removing previously produced cis P-tau could be a suitable approach in treating TBI in order to prevent tauopathies and future neurodegeneration.

Repetitive Suicidal Behaviors in a Case With a New Mutation of Wolfram Syndrome: A Jump From the Gene to the Behavior.

Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disease with variable symptoms, including neuropsychiatric manifestations. A 26-year-old man was reported with classic symptoms of WS and repetitive psychiatric hospitalizations and at least 16 suicidal attempts. The genetic study demonstrated a novel homozygous stop-codon mutation on the WFS1 gene. This special type of mutation may be related to repetitive suicidal behaviors in this case of WS. Psychological support should be a routine practice in patients with WS.

Association between TBXT rs2305089 polymorphism and chordoma in Iranian patients identified by a developed T-ARMS-PCR assay.

BACKGROUND: Chordoma is a locally aggressive bone tumor with a high capability of recurrence. Because chordoma often occurs at critical locations next to neurovascular structures, there is an urgent need to introduce validated biomarkers. T-box transcription factor T (TBXT; OMIM: 601397) plays an important role in the pathogenesis and survival of chordoma cells. METHODS: Herein, we aimed to show whether rs2305089 polymorphism is correlated with chordoma in the Iranian population. In order to detect rs2305089, tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) was used. In total, 19 chordoma patients and 108 normal healthy individuals were recruited and screened using T-ARMS-PCR. The results were subsequently validated by Sanger sequencing. RESULTS: The genotype distributions and allele frequencies were significantly different among the patient and healthy groups (p-value <0.05). The A allele of rs2305089 showed a significant positive association with chordoma risk (p-value <0.05). DNA sequencing verified the T-ARMS-PCR results as well. This study demonstrated the association between TBXT rs2305089 and chordoma in an Iranian population using a simple, accurate, and cost-effective T-ARMS-PCR assay. CONCLUSIONS: Our results were in line with those of previous studies showing that TBXT rs2305089 is associated with chordoma development. We also developed an efficient T-ARMS-PCR assay to determine the genotype of rs2305089.